Lamins: Nuclear intermediate filament proteins with fundamental functions in nuclear mechanics and genome regulation

Annual Review of Biochemistry

Volumn 84, Issue , 2015, Pages 131-164

  Gruenbaum, Yosef ^a   Foisner, Roland ^b  

^a HEBREW UNIVERSITY OF JERUSALEM   (Israel)

^b MEDICAL UNIVERSITY OF VIENNA   (Austria)

Author keywords

Chromatin; Intermediate filament; Laminopathies; Lamins; Nuclear envelope; Nuclear mechanics; Nuclear organization

Indexed keywords

LAMIN A; LAMIN B; CHROMATIN; LAMIN;

AGING; ARTICLE; CELL DIFFERENTIATION; CELL NUCLEUS; CHROMATIN; CYTOSKELETON; EVOLUTION; GENE CONTROL; GENE EXPRESSION; GENE MUTATION; GENETIC REGULATION; GENETIC VARIABILITY; GENOMIC INSTABILITY; HUMAN; INTRACELLULAR SIGNALING; LAMINOPATHY; METABOLISM; MUSCULAR DYSTROPHY; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROGERIA; PROTEIN ASSEMBLY; PROTEIN BINDING; PROTEIN FUNCTION; STEM CELL; TISSUE SPECIFICITY; WERNER SYNDROME; ANIMAL; CHEMISTRY; GENE EXPRESSION REGULATION; GENETICS; PATHOLOGY;

ANIMALS; CELL NUCLEUS; CHROMATIN; GENE EXPRESSION REGULATION; HUMANS; LAMINS; PROGERIA;

EID: 84930719986     PISSN: 00664154     EISSN: 15454509     Source Type: Book Series    
DOI: 10.1146/annurev-biochem-060614-034115     Document Type: Article

References (310)

1. Pappas GD. 1956. The fine structure of the nuclear envelope of Amoeba proteus. J. Biophys. Biochem. Cytol. 2(Suppl.):431-34
2. Fawcett DW. 1966. On the occurrence of a fibrous lamina on the inner aspect of the nuclear envelope in certain cells of vertebrates. Am. J. Anat. 119:129-45
3. Aaronson RP, Blobel G. 1975. Isolation of nuclear pore complexes in association with a lamina. PNAS 72:1007-11
4. Gerace L, Blum A, Blobel G. 1978. Immunocytochemical localization of the major polypeptides of the nuclear pore complex-lamina fraction. Interphase and mitotic distribution. J. Cell Biol. 79:546-66
5. McKeon FD, Kirschner MW, Caput D. 1986. Homologies in both primary and secondary structure between nuclear envelope and intermediate filament proteins. Nature 319:463-68
6. Fisher DZ, Chaudhary N, Blobel G. 1986. cDNA sequencing of nuclear lamins A and C reveals primary and secondary structural homology to intermediate filament proteins. PNAS 83:6450-54
7. Krohne G, Wolin SL, McKeon FD, Franke WW, Kirschner MW. 1987. Nuclear lamin LI of Xenopus laevis: cDNA cloning, amino acid sequence and binding specificity of a member of the lamin B subfamily. EMBO J. 6:3801-08
8. Gruenbaum Y, Landesman Y, Drees B, Bare JW, Saumweber H, et al. 1988. Drosophila nuclear lamin precursor Dm0 is translated from either of two developmentally regulated mRNA species apparently encoded by a single gene. J. Cell Biol. 106:585-96
9. Lehner CF, Stick R, Eppenberger HM, Nigg EA. 1987. Differential expression of nuclear lamin proteins during chicken development. J. Cell Biol. 105:577-87
10. Rober RA, Weber K, Osborn M. 1989. Differential timing of nuclear lamin A/C expression in the various organs of the mouse embryo and the young animal: a developmental study. Development 105:365-78
11. Stewart C, Burke B. 1987. Teratocarcinoma stem cells and early mouse embryos contain only a single major lamin polypeptide closely resembling lamin B. Cell 51:383-92
12. Rusinol AE, Sinensky MS. 2006. Farnesylated lamins, progeroid syndromes and farnesyl transferase inhibitors. J. Cell Sci. 119:3265-72
13. Firmbach-Kraft I, Stick R. 1993. The role of CaaX-dependent modifications in membrane association of Xenopus nuclear lamin B3 during meiosis and the fate of B3 in transfected mitotic cells. J. Cell Biol. 123:1661-70
14. Adam SA, Butin-Israeli V, Cleland MM, Shimi T, Goldman RD. 2013. Disruption of lamin B1 and lamin B2 processing and localization by farnesyltransferase inhibitors. Nucleus 4:142-50
15. Moir RD, Yoon M, Khuon S, Goldman RD. 2000. Nuclear lamins A and B1: different pathways of assembly during nuclear envelope formation in living cells. J. Cell Biol. 151:1155-68
16. Naetar N, Korbei B, Kozlov S, Kerenyi MA, Dorner D, et al. 2008. Loss of nucleoplasmic LAP2α-lamin A complexes causes erythroid and epidermal progenitor hyperproliferation. Nat. Cell Biol. 10:1341-48
17. Lyakhovetsky R, Gruenbaum Y. 2014. Studying lamins in invertebrate models. Adv. Exp. Med. Biol. 773:245-62
18. Zimek A, Weber K. 2011. Flanking genes of an essential gene give information about the evolution of metazoa. Eur. J. Cell Biol. 90:1263-72
19. Peter A, Stick R. 2012. Evolution of the lamin protein family: what introns can tell. Nucleus 3:44-59
20. Bank EM, Gruenbaum Y. 2011. Caenorhabditis elegans as a model system for studying the nuclear lamina and laminopathic diseases. Nucleus 2:350-57
21. Riemer D, Wang J, Zimek A, Swalla BJ, Weber K. 2000. Tunicates have unusual nuclear lamins with a large deletion in the carboxyterminal tail domain. Gene 255:317-25
22. Riemer D, Weber K. 1994. The organization of the gene for Drosophila lamin C: limited homology with vertebrate lamin genes and lack of homology versus the Drosophila lamin Dmo gene. Eur. J. Cell Biol. 63:299-306
23. Hofemeister H, Kuhn C, Franke WW, Weber K, Stick R. 2002. Conservation of the gene structure and membrane-targeting signals of germ cell-specific lamin LIII in amphibians and fish. Eur. J. Cell Biol. 81:51-60
24. Zimek A, Stick R, Weber K. 2003. Genes coding for intermediate filament proteins: common features and unexpected differences in the genomes of humans and the teleost fish Fugu rubripes. J. Cell Sci. 116:2295-302
25. Krüger A, Batsios P, Baumann O, Luckert E, Schwarz H, et al. 2012. Characterization of NE81, the first lamin-like nucleoskeleton protein in a unicellular organism. Mol. Biol. Cell 23:360-70
26. DuBois KN, Alsford S, Holden JM, Buisson J, Swiderski M, et al. 2012. NUP-1 is a large coiled-coil nucleoskeletal protein in trypanosomes with lamin-like functions. PLOS Biol. 10:e1001287
27. Ciska M, Masuda K, Moreno Díaz de la Espina S. 2013. Lamin-like analogues in plants: the characterization of NMCP1 in Allium cepa. J. Exp. Bot. 64:1553-64
28. Graumann K. 2014. Evidence for LINC1-sun associations at the plant nuclear periphery. PLOS ONE 9:e93406
29. Steinert PM, Roop DR. 1988. Molecular and cellular biology of intermediate filaments. Annu. Rev. Biochem. 57:593-625
30. Herrmann H, Aebi U. 2004. Intermediate filaments: molecular structure, assembly mechanism, and integration into functionally distinct intracellular scaffolds. Annu. Rev. Biochem. 74:749-89
31. Aebi U, Cohn J, Buhle L, Gerace L. 1986. The nuclear lamina is a meshwork of intermediate-type filaments. Nature 323:560-64
32. Dittmer TA, Misteli T. 2011. The lamin protein family. Genome Biol. 12:222
33. Heitlinger E, Peter M, Haner M, Lustig A, Aebi U, Nigg EA. 1991. Expression of chicken lamin B2 in Escherichia coli: characterization of its structure, assembly, and molecular interactions. J. Cell Biol. 113:485-95
34. Klapper M, Exner K, Kempf A, Gehrig C, Stuurman N, et al. 1997. Assembly of A- and B-type lamins studied in vivo with the baculovirus system. J. Cell Sci. 110:2519-32
35. Karabinos A, Schunemann J, Meyer M, Aebi U, Weber K. 2003. The single nuclear lamin of Caenorhabditis elegans forms in vitro stable intermediate filaments and paracrystals with a reduced axial periodicity. J. Mol. Biol. 325:241-47
36. Foeger N, Wiesel N, Lotsch D, Mucke N, Kreplak L, et al. 2006. Solubility properties and specific assembly pathways of the B-type lamin from Caenorhabditis elegans. J. Struct. Biol. 155:340-50
37. Ben-Harush K, Wiesel N, Frenkiel-Krispin D, Moeller D, Soreq E, et al. 2009. The supramolecular organization of the C. Elegans nuclear lamin filament. J. Mol. Biol. 386:1392-402
38. Grossmann E, Dahan I, Stick R, Goldberg MW, Gruenbaum Y, Medalia O. 2011. Filament assembly of ectopically expressed C. Elegans lamin within Xenopus oocytes. J. Struct. Biol. 177:113-18
39. Taimen P, Pfleghaar K, Shimi T, Möller D, Ben-Harush K, et al. 2009. A progeriamutation reveals functions for lamin A in nuclear assembly, architecture, and chromosome organization. PNAS 106:20788-93
40. Zwerger M, Jaalouk DE, Lombardi ML, Isermann P, Mauermann M, et al. 2013. Myopathic lamin mutations impair nuclear stability in cells and tissue and disrupt nucleo-cytoskeletal coupling. Hum. Mol. Genet. 22:2335-49
41. Bank EM, Ben-Harush K, Wiesel-Motiuk N, Barkan R, Feinstein N, et al. 2011. Alaminopathic mutation disrupting lamin filament assembly causes disease-like phenotypes in Caenorhabditis elegans. Mol. Biol. Cell 22:2716-28
42. Wiesel N, Mattout A, Melcer S, Melamed-Book N, Herrmann H, et al. 2008. Laminopathic mutations interfere with the assembly, localization, and dynamics of nuclear lamins. PNAS 105:180-85
43. Schirmer EC, Guan T, Gerace L. 2001. Involvement of the lamin rod domain in heterotypic lamin interactions important for nuclear organization. J. Cell Biol. 153:479-90
44. Kolb T, Maass K, Hergt M, Aebi U, Herrmann H. 2011. Lamin A and lamin C form homodimers and coexist in higher complex forms both in the nucleoplasmic fraction and in the lamina of cultured human cells. Nucleus 2:425-33
45. Fong LG, Ng JK, Lammerding J, Vickers TA, Meta M, et al. 2006. Prelamin A and lamin A appear to be dispensable in the nuclear lamina. J. Clin. Investig. 116:743-52
46. Kapinos LE, Schumacher J, Mücke N, Machaidze G, Burkhard P, et al. 2010. Characterization of the head-to-tail overlap complexes formed by human lamin A, B1 and B2 "half-minilamin" dimers. J. Mol. Biol. 396:719-31
47. Goldberg MW, Huttenlauch I, Hutchison CJ, Stick R. 2008. Filaments made from A- and B-type lamins differ in structure and organization. J. Cell Sci. 121:215-25
48. Sullivan T, Escalante-Alcalde D, Bhatt H, Anver M, Bhat N, et al. 1999. Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy. J. Cell Biol. 147:913-20
49. Kim Y, Sharov AA, McDole K, Cheng M, Hao H, et al. 2011. Mouse B-type lamins are required for proper organogenesis but not by embryonic stem cells. Science 334:1706-10
50. Yang SH, Chang SY, Yin L, Tu Y, Hu Y, et al. 2011. An absence of both lamin B1 and lamin B2 in keratinocytes has no effect on cell proliferation or the development of skin and hair. Hum. Mol. Genet. 20:3537-44
51. Guo Y, Kim Y, Shimi T, Goldman RD, Zheng Y. 2014. Concentration-dependent lamin assembly and its roles in the localization of other nuclear proteins. Mol. Biol. Cell 25:1287-97
52. Shimi T, Pfleghaar K, Kojima S, Pack CG, Solovei I, et al. 2008. The A- and B-type nuclear lamin networks: microdomains involved in chromatin organization and transcription. Genes Dev. 22:3409-21
53. Funkhouser CM, Sknepnek R, Shimi T, Goldman AE, Goldman RD, Olvera de la Cruz M. 2013. Mechanical model of blebbing in nuclear lamin meshworks. PNAS 110:3248-53
54. Liu J, Rolef-Ben Shahar T, Riemer D, Spann P, Treinin M, et al. 2000. Essential roles for Caenorhabditis elegans lamin gene in nuclear organization, cell cycle progression, and spatial organization of nuclear pore complexes. Mol. Biol. Cell 11:3937-47
55. Lenz-Böhme B, Wismar J, Fuchs S, Reifegerste R, Buchner E, et al. 1997. Insertional mutation of the Drosophila nuclear lamin Dm0 gene results in defective nuclear envelopes, clustering of nuclear pore complexes, and accumulation of annulate lamellae. J. Cell Biol. 137:1001-16
56. Schulze SR, Curio-Penny B, Speese S, Dialynas G, Cryderman DE, et al. 2009. A comparative study of Drosophila and human A-type lamins. PLOS ONE 4:e7564
57. van Engelen BG, Muchir A, Hutchison CJ, van der Kooi AJ, Bonne G, Lammens M. 2005. The lethal phenotype of a homozygous nonsense mutation in the lamin A/C gene. Neurology 64:374-76
58. Davidson PM, Lammerding J. 2014. Broken nuclei-lamins, nuclear mechanics, and disease. Trends Cell Biol. 24:247-56
59. Broers JL, Peeters EA, Kuijpers HJ, Endert J, Bouten CV, et al. 2004. Decreased mechanical stiffness in LMNA-/- cells is caused by defective nucleo-cytoskeletal integrity. Implications for the development of laminopathies. Hum. Mol. Genet. 13:2567-80
60. Dahl KN, Kahn SM, Wilson KL, Discher DE. 2004. The nuclear envelope lamina network has elasticity and a compressibility limit suggestive of a molecular shock absorber. J. Cell Sci. 117:4779-86
61. Lammerding J, Fong LG, Ji JY, Reue K, Stewart CL, et al. 2006. Lamins A and C but not lamin B1 regulate nuclear mechanics. J. Biol. Chem. 281:25768-80
62. Lammerding J, Schulze PC, Takahashi T, Kozlov S, Sullivan T, et al. 2004. Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction. J. Clin. Investig. 113:370-78
63. Shin JW, Spinler KR, Swift J, Chasis JA, Mohandas N, Discher DE. 2013. Lamins regulate cell trafficking and lineage maturation of adult human hematopoietic cells. PNAS 110:18892-97
64. Swift J, Ivanovska IL, Buxboim A, Harada T, Dingal PC, et al. 2013. Nuclear lamin-A scales with tissue stiffness and enhances matrix-directed differentiation. Science 341:1240104
65. Harada T, Swift J, Irianto J, Shin JW, Spinler KR, et al. 2014. Nuclear lamin stiffness is a barrier to 3D migration, but softness can limit survival. J. Cell Biol. 204:669-82
66. Rowat AC, Jaalouk DE, Zwerger M, Ung WL, Eydelnant IA, et al. 2013. Nuclear envelope composition determines the ability of neutrophil-type cells to passage through micron-scale constrictions. J. Biol. Chem. 288:8610-18
67. De Vos WH, Houben F, Kamps M, Malhas A, Verheyen F, et al. 2011. Repetitive disruptions of the nuclear envelope invoke temporary loss of cellular compartmentalization in laminopathies. Hum. Mol. Genet. 20:4175-86
68. Hatch EM, Fischer AH, Deerinck TJ, Hetzer MW. 2013. Catastrophic nuclear envelope collapse in cancer cell micronuclei. Cell 154:47-60
69. Vargas JD, Hatch EM, Anderson DJ, Hetzer MW. 2012. Transient nuclear envelope rupturing during interphase in human cancer cells. Nucleus 3:88-100
70. Ferrera D, Canale C, Marotta R, Mazzaro N, Gritti M, et al. 2014. Lamin B1 overexpression increases nuclear rigidity in autosomal dominant leukodystrophy fibroblasts. FASEB J. 28:3906-18
71. Lombardi ML, Jaalouk DE, Shanahan CM, Burke B, Roux KJ, Lammerding J. 2011. The interaction between nesprins and sun proteins at the nuclear envelope is critical for force transmission between the nucleus and cytoskeleton. J. Biol. Chem. 286:26743-53
72. Bainer R, Weaver V. 2013. Cell biology. Strength under tension. Science 341:965-66
73. Lammerding J, Hsiao J, Schulze PC, Kozlov S, Stewart CL, Lee RT. 2005. Abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells. J. Cell Biol. 170:781-91
74. Ho CY, Jaalouk DE, Vartiainen MK, Lammerding J. 2013. Lamin A/C and emerin regulateMKL1-SRF activity by modulating actin dynamics. Nature 497:507-11
75. Guilluy C, Osborne LD, Van Landeghem L, Sharek L, Superfine R, et al. 2014. Isolated nuclei adapt to force and reveal a mechanotransduction pathway in the nucleus. Nat. Cell Biol. 16:376-81
76. Belmont AS, Zhai Y, Thilenius A. 1993. Lamin B distribution and association with peripheral chromatin revealed by optical sectioning and electron microscopy tomography. J. Cell Biol. 123:1671-85
77. Cremer T, Cremer M. 2010. Chromosome territories. Cold Spring Harb. Perspect. Biol. 2:a003889
78. Gruenbaum Y, Hochstrasser M, Mathog D, Saumweber H, Agard DA, Sedat JW. 1984. Spatial organization of the Drosophila nucleus: a three-dimensional cytogenetic study. J. Cell Sci. Suppl. 1:223-34
79. Croft JA, Bridger JM, Boyle S, Perry P, Teague P, Bickmore WA. 1999. Differences in the localization and morphology of chromosomes in the human nucleus. J. Cell Biol. 145:1119-31
80. Zuleger N, Robson MI, Schirmer EC. 2011. The nuclear envelope as a chromatin organizer. Nucleus 2:339-49
81. Pickersgill H, Kalverda B, de Wit E, Talhout W, Fornerod M, van Steensel B. 2006. Characterization of the Drosophila melanogaster genome at the nuclear lamina. Nat. Genet. 38:1005-14
82. Guelen L, Pagie L, Brasset E, Meuleman W, Faza MB, et al. 2008. Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions. Nature 453:948-51
83. Peric-Hupkes D, Meuleman W, Pagie L, Bruggeman SW, Solovei I, et al. 2010. Molecular maps of the reorganization of genome-nuclear lamina interactions during differentiation. Mol. Cell 38:603-13
84. Meuleman W, Peric-Hupkes D, Kind J, Beaudry JB, Pagie L, et al. 2013. Constitutive nuclear lamina-genome interactions are highly conserved and associated with A/T-rich sequence. Genome Res. 23:270-80
85. Kind J, van Steensel B. 2014. Stochastic genome-nuclear lamina interactions: modulating roles of lamin A and BAF. Nucleus 5:124-30
86. Sadaie M, Salama R, Carroll T, Tomimatsu K, Chandra T, et al. 2013. Redistribution of the lamin B1 genomic binding profile affects rearrangement of heterochromatic domains and SAHF formation during senescence. Genes Dev. 27:1800-8
87. Shah PP, Donahue G, Otte GL, Capell BC, Nelson DM, et al. 2013. Lamin B1 depletion in senescent cells triggers large-scale changes in gene expression and the chromatin landscape. Genes Dev. 27:1787-99
88. Lund E, Oldenburg AR, Delbarre E, Freberg CT, Duband-Goulet I, et al. 2013. Lamin A/C-promoter interactions specify chromatin state-dependent transcription outcomes. Genome Res. 23:1580-89
89. Towbin BD, Gonzalez-Aguilera C, Sack R, Gaidatzis D, Kalck V, et al. 2012. Step-wise methylation of histone H3K9 positions heterochromatin at the nuclear periphery. Cell 150:934-47
90. Ikegami K, Egelhofer TA, Strome S, Lieb JD. 2010. Caenorhabditis elegans chromosome arms are anchored to the nuclear membrane via discontinuous association with LEM-2. Genome Biol. 11:R120
91. Finlan LE, Sproul D, Thomson I, Boyle S, Kerr E, et al. 2008. Recruitment to the nuclear periphery can alter expression of genes in human cells. PLOS Genet. 4:e1000039
92. Kumaran RI, Spector DL. 2008. A genetic locus targeted to the nuclear periphery in living cells maintains its transcriptional competence. J. Cell Biol. 180:51-65
93. Reddy KL, Zullo JM, Bertolino E, Singh H. 2008. Transcriptional repression mediated by repositioning of genes to the nuclear lamina. Nature 452:243-47
94. Dialynas G, Speese S, Budnik V, Geyer PK, Wallrath LL. 2010. The role of Drosophila lamin C inmuscle function and gene expression. Development 137:3067-77
95. Goldberg M, Harel A, Brandeis M, Rechsteiner T, Richmond TJ, et al. 1999. The tail domain of lamin Dm0 binds histones H2A and H2B. PNAS 96:2852-57
96. Mattout A, Goldberg M, Tzur Y, Margalit A, Gruenbaum Y. 2007. Specific and conserved sequences in D. melanogaster and C. Elegans lamins and histoneH2A mediate the attachment of lamins to chromosomes. J. Cell Sci. 120:77-85
97. Taniura H, Glass C, Gerace L. 1995. A chromatin binding site in the tail domain of nuclear lamins that interacts with core histones. J. Cell Biol. 131:33-44
98. Yuan J, Simos G, Blobel G, Georgatos SD. 1991. Binding of lamin A to polynucleosomes. J. Biol. Chem. 266:9211-15
99. Luderus ME, de Graaf A, Mattia E, den Blaauwen JL, Grande MA, et al. 1992. Binding of matrix attachment regions to lamin B1. Cell 70:949-59
100. Luderus ME, den Blaauwen JL, de Smit OJ, Compton DA, van Driel R. 1994. Binding of matrix attachment regions to lamin polymers involves single-stranded regions and the minor groove. Mol. Cell. Biol. 14:6297-305
101. Zhao K, Harel A, Stuurman N, Guedalia D, Gruenbaum Y. 1996. Binding of matrix attachment regions to nuclear lamin is mediated by the rod domain and depends on the lamin polymerization state. FEBS Lett. 380:161-64
102. Stierle V, Couprie J, Ostlund C, Krimm I, Zinn-Justin S, et al. 2003. The carboxyl-terminal region common to lamins A and C contains a DNA binding domain. Biochemistry 42:4819-28
103. Glass CA, Glass JR, Taniura H, Hasel KW, Blevitt JM, Gerace L. 1993. The alpha-helical rod domain of human lamins A and C contains a chromatin binding site. EMBO J. 12:4413-24
104. Malhas A, Lee CF, Sanders R, Saunders NJ, Vaux DJ. 2007. Defects in lamin B1 expression or processing affect interphase chromosome position and gene expression. J. Cell Biol. 176:593-603
105. Solovei I, Wang AS, Thanisch K, Schmidt CS, Krebs S, et al. 2013. LBR and lamin A/C sequentially tether peripheral heterochromatin and inversely regulate differentiation. Cell 152:584-98
106. Cohen M, Tzur YB, Neufeld E, Feinstein N, Delannoy MR, et al. 2002. Transmission electron microscope studies of the nuclear envelope in Caenorhabditis elegans embryos. J. Struct. Biol. 140:232-40
107. Lee DC, Welton KL, Smith ED, Kennedy BK. 2009. A-type nuclear lamins act as transcriptional repressors when targeted to promoters. Exp. Cell Res. 315:996-1007
108. Ye Q, Worman HJ. 1996. Interaction between an integral protein of the nuclear envelope inner membrane and human chromodomain proteins homologous to Drosophila HP1. J. Biol. Chem. 271:14653-56
109. Hirano Y, Hizume K, Kimura H, Takeyasu K, Haraguchi T, Hiraoka Y. 2012. Lamin B receptor recognizes specificmodifications of histoneH4 in heterochromatin formation. J. Biol. Chem. 287:42654-63
110. Zullo JM, Demarco IA, Pique-Regi R, Gaffney DJ, Epstein CB, et al. 2012. DNA sequence-dependent compartmentalization and silencing of chromatin at the nuclear lamina. Cell 149:1474-87
111. Nili E, Cojocaru GS, Kalma Y, Ginsberg D, Copeland NG, et al. 2001. Nuclear membrane protein LAP2β mediates transcriptional repression alone and together with its binding partner GCL (germcell- less). J. Cell Sci. 114:3297-307
112. Somech R, Shaklai S, Geller O, Amariglio N, Simon AJ, et al. 2005. The nuclear-envelope protein and transcriptional repressor LAP2β interacts with HDAC3 at the nuclear periphery, and induces histone H4 deacetylation. J. Cell Sci. 118:4017-25
113. Demmerle J, Koch AJ, Holaska JM. 2012. The nuclear envelope protein emerin binds directly to histone deacetylase 3 (HDAC3) and activates HDAC3 activity. J. Biol. Chem. 287:22080-88
114. Brachner A, Foisner R. 2011. Evolvement ofLEMproteins as chromatin tethers at the nuclear periphery. Biochem. Soc. Trans. 39:1735-41
115. Margalit A, Brachner A, Gotzmann J, Foisner R, Gruenbaum Y. 2007. Barrier-to-autointegration factor-a BAFfling little protein. Trends Cell Biol. 17:202-8
116. Amendola M, van Steensel B. 2014. Mechanisms and dynamics of nuclear lamina-genome interactions. Curr. Opin. Cell Biol. 28C:61-68
117. Yaffe E, Tanay A. 2011. Probabilistic modeling of Hi-C contact maps eliminates systematic biases to characterize global chromosomal architecture. Nat. Genet. 43:1059-65
118. Akhtar W, de Jong J, Pindyurin AV, Pagie L, Meuleman W, et al. 2013. Chromatin position effects assayed by thousands of reporters integrated in parallel. Cell 154:914-27
119. Ottaviani A, Rival-Gervier S, Boussouar A, Foerster AM, Rondier D, et al. 2009. The D4Z4 macrosatellite repeat acts as aCTCFandA-type lamins-dependent insulator in facio-scapulo-humeral dystrophy. PLOS Genet. 5:e1000394
120. Ottaviani A, Schluth-Bolard C, Rival-Gervier S, Boussouar A, Rondier D, et al. 2009. Identification of a perinuclear positioning element in human subtelomeres that requires A-type lamins and CTCF. EMBO J. 28:2428-36
121. Kind J, Pagie L, Ortabozkoyun H, Boyle S, de Vries SS, et al. 2013. Single-cell dynamics of genomenuclear lamina interactions. Cell 153:178-92
122. Bian Q, Khanna N, Alvikas J, Belmont AS. 2013. β-Globin cis-elements determine differential nuclear targeting through epigenetic modifications. J. Cell Biol. 203:767-83
123. Milon BC, Cheng H, Tselebrovsky MV, Lavrov SA, Nenasheva VV, et al. 2012. Role of histone deacetylases in gene regulation at nuclear lamina. PLOS ONE 7:e49692
124. Meister P, Towbin BD, Pike BL, Ponti A, Gasser SM. 2010. The spatial dynamics of tissue-specific promoters during C. Elegans development. Genes Dev. 24:766-82
125. Towbin BD, Meister P, Pike BL, Gasser SM. 2010. Repetitive transgenes in C. Elegans accumulate heterochromatic marks and are sequestered at the nuclear envelope in a copy-number- and lamindependent manner. Cold Spring Harb. Symp. Quant. Biol. 75:555-65
126. Shevelyov YY, Lavrov SA, Mikhaylova LM, Nurminsky ID, Kulathinal RJ, et al. 2009. The B-type lamin is required for somatic repression of testis-specific gene clusters. PNAS 106:3282-87
127. Kohwi M, Lupton JR, Lai SL, Miller MR, Doe CQ. 2013. Developmentally regulated subnuclear genome reorganization restricts neural progenitor competence in Drosophila. Cell 152:97-108
128. Clowney EJ, LeGros MA, Mosley CP, Clowney FG, Markenskoff-Papadimitriou EC, et al. 2012. Nuclear aggregation of olfactory receptor genes governs their monogenic expression. Cell 151:724-37
129. Demmerle J, Koch AJ, Holaska JM. 2013. Emerin and histone deacetylase 3 (HDAC3) cooperatively regulate expression and nuclear positions of MyoD, Myf5, andPax7 genes duringmyogenesis. Chromosome Res. 21:765-79
130. Camps J, Wangsa D, Falke M, Brown M, Case CM, et al. 2014. Loss of lamin B1 results in prolongation of S phase and decondensation of chromosome territories. FASEB J. 28:3423-34
131. Poleshko A, Mansfield KM, Burlingame CC, Andrake MD, Shah NR, Katz RA. 2013. The human protein PRR14 tethers heterochromatin to the nuclear lamina during interphase and mitotic exit. Cell Rep. 5:292-301
132. Schirmer EC, Florens L, Guan T, Yates JR 3rd, Gerace L. 2003. Nuclear membrane proteins with potential disease links found by subtractive proteomics. Science 301:1380-82
133. Korfali N, Wilkie GS, Swanson SK, Srsen V, de LasHeras J, et al. 2012. The nuclear envelope proteome differs notably between tissues. Nucleus 3:552-64
134. Schirmer EC, Foisner R. 2007. Proteins that associate with lamins: many faces, many functions. Exp. Cell Res. 313:2167-79
135. Wilson KL, Foisner R. 2010. Lamin-binding proteins. Cold Spring Harb. Perspect. Biol. 2:a000554
136. Foisner R, Gerace L. 1993. Integral membrane proteins of the nuclear envelope interact with lamins and chromosomes, and binding is modulated by mitotic phosphorylation. Cell 73:1267-79
137. Martin L, Crimaudo C, Gerace L. 1995. cDNA cloning and characterization of lamina-associated polypeptide 1C (LAP1C), an integral protein of the inner nuclear membrane. J. Biol. Chem. 270:8822-28
138. Goodchild RE, Dauer WT. 2005. The AAA+ protein torsinA interacts with a conserved domain present in LAP1 and a novel ER protein. J. Cell Biol. 168:855-62
139. Shin JY, Mendez-Lopez I, Wang Y, Hays AP, Tanji K, et al. 2013. Lamina-associated polypeptide-1 interacts with the muscular dystrophy protein emerin and is essential for skeletal muscle maintenance. Dev. Cell 26:591-603
140. Zhao C, Brown RS, Chase AR, Eisele MR, Schlieker C. 2013. Regulation of Torsin ATPases by LAP1 and LULL1. PNAS 110:E1545-54
141. Kim CE, Perez A, Perkins G, Ellisman MH, Dauer WT. 2010. A molecular mechanism underlying the neural-specific defect in torsinA mutant mice. PNAS 107:9861-66
142. Kayman-Kurekci G, Talim B, Korkusuz P, Sayar N, Sarioglu T, et al. 2014. Mutation in TOR1AIP1 encoding LAP1B in a form of muscular dystrophy: a novel gene related to nuclear envelopathies. Neuromuscul. Disord. 24:624-33
143. Olins AL, Rhodes G, Welch DB, Zwerger M, Olins DE. 2010. Lamin B receptor: multi-tasking at the nuclear envelope. Nucleus 1:53-70
144. Hoffmann K, Dreger CK, Olins AL, Olins DE, Shultz LD, et al. 2002. Mutations in the gene encoding the lamin B receptor produce an altered nuclear morphology in granulocytes (Pelger-Huet anomaly). Nat. Genet. 31:410-14
145. Waterham HR, Koster J, Mooyer P, van Noort G, Kelley RI, et al. 2003. Autosomal recessive HEM/Greenberg skeletal dysplasia is caused by 3β-hydroxysterol-14-reductase deficiency due to mutations in the lamin B receptor gene. Am. J. Hum. Genet. 72:1013-17
146. Mejat A, Misteli T. 2010. LINC complexes in health and disease. Nucleus 1:40-52
147. Rothballer A, Schwartz TU, Kutay U. 2013. LINCing complex functions at the nuclear envelope: what the molecular architecture of the LINC complex can reveal about its function. Nucleus 4:29-36
148. Tapley EC, Starr DA. 2013. Connecting the nucleus to the cytoskeleton by SUN-KASH bridges across the nuclear envelope. Curr. Opin. Cell Biol. 25:57-62
149. Crisp M, Liu Q, Roux K, Rattner JB, Shanahan C, et al. 2006. Coupling of the nucleus and cytoplasm: role of the LINC complex. J. Cell Biol. 172:41-53
150. Sosa BA, Rothballer A, Kutay U, Schwartz TU. 2012. LINC complexes form by binding of three KASH peptides to domain interfaces of trimeric SUN proteins. Cell 149:1035-47
151. Penkner A, Tang L, Novatchkova M, Ladurner M, Fridkin A, et al. 2007. The nuclear envelope protein Matefin/SUN-1 is required for homologous pairing in C. Elegans meiosis. Dev. Cell 12:873-85
152. Penkner AM, Fridkin A, Gloggnitzer J, Baudrimont A, Machacek T, et al. 2009. Meiotic chromosome homology search involves modifications of the nuclear envelope proteinMatefin/SUN-1. Cell 139:920-33
153. Sato A, Isaac B, Phillips CM, Rillo R, Carlton PM, et al. 2009. Cytoskeletal forces span the nuclear envelope to coordinate meiotic chromosome pairing and synapsis. Cell 139:907-19
154. Ding X, Xu R, Yu J, Xu T, Zhuang Y, Han M. 2007. SUN1 is required for telomere attachment to nuclear envelope and gametogenesis in mice. Dev. Cell 12:863-72
155. Link J, Leubner M, Schmitt J, Gob E, Benavente R, et al. 2014. Analysis of meiosis in SUN1 deficient mice reveals a distinct role of SUN2 in mammalian meiotic LINC complex formation and function. PLOS Genet. 10:e1004099
156. Horn HF, Kim DI, Wright GD, Wong ES, Stewart CL, et al. 2013. A mammalian KASH domain protein coupling meiotic chromosomes to the cytoskeleton. J. Cell Biol. 202:1023-39
157. Morimoto A, Shibuya H, Zhu X, Kim J, Ishiguro K, et al. 2012. A conserved KASH domain protein associates with telomeres, SUN1, and dynactin during mammalian meiosis. J. Cell Biol. 198:165-72
158. Laguri C, Gilquin B, Wolff N, Romi-Lebrun R, Courchay K, et al. 2001. Structural characterization of the LEM motif common to three human inner nuclear membrane proteins. Structure 9:503-11
159. Lin F, Blake DL, Callebaut I, Skerjanc IS, Holmer L, et al. 2000. MAN1, an inner nuclear membrane protein that shares the LEM domain with lamina-associated polypeptide 2 and emerin. J. Biol. Chem. 275:4840-47
160. Cai M, Huang Y, Ghirlando R, Wilson KL, Craigie R, Clore GM. 2001. Solution structure of the constant region of nuclear envelope protein LAP2 reveals two LEM-domain structures: One binds BAF and the other binds DNA. EMBO J. 20:4399-407
161. Cai M, Huang Y, Suh JY, Louis JM, Ghirlando R, et al. 2007. Solution NMR structure of the barrierto- autointegration factor-emerin complex. J. Biol. Chem. 282:14525-35
162. Liu J, Lee KK, Segura-Totten M, Neufeld E, Wilson KL, Gruenbaum Y. 2003. MAN1 and emerin have overlapping function(s) essential for chromosome segregation and cell division in Caenorhabditis elegans. PNAS 100:4598-603
163. Barkan R, Zahand AJ, Sharabi K, Lamm AT, Feinstein N, et al. 2012. Ce-emerin and LEM-2: essential roles in Caenorhabditis elegans development, muscle function, and mitosis. Mol. Biol. Cell 23:543-52
164. Bione S, Maestrini E, Rivella S, Mancini M, Regis S, et al. 1994. Identification of a novel X-linked gene responsible for Emery-Dreifuss muscular dystrophy. Nat. Genet. 8:323-27
165. Melcon G, Kozlov S, Cutler DA, Sullivan T, Hernandez L, et al. 2006. Loss of emerin at the nuclear envelope disrupts the Rb1/E2F and MyoD pathways during muscle regeneration. Hum. Mol. Genet. 15:637-51
166. Caputo S, Couprie J, Duband-Goulet I, Konde E, Lin F, et al. 2006. The carboxyl-terminal nucleoplasmic region of MAN1 exhibits a DNA binding winged helix domain. J. Biol. Chem. 281:18208-15
167. Markiewicz E, Tilgner K, Barker N, van de Wetering M, Clevers H, et al. 2006. The inner nuclear membrane protein emerin regulates β-catenin activity by restricting its accumulation in the nucleus. EMBO J. 25:3275-85
168. Tilgner K, Wojciechowicz K, Jahoda C, Hutchison C, Markiewicz E. 2009. Dynamic complexes of A-type lamins and emerin influence adipogenic capacity of the cell via nucleocytoplasmic distribution of β-catenin. J. Cell Sci. 122:401-13
169. Dedeic Z, Cetera M, Cohen TV, Holaska JM. 2011. Emerin inhibits Lmo7 binding to the Pax3 and MyoD promoters and expression of myoblast proliferation genes. J. Cell Sci. 124:1691-702
170. Holaska JM, Rais-Bahrami S, Wilson KL. 2006. Lmo7 is an emerin-binding protein that regulates the transcription of emerin and many other muscle-relevant genes. Hum. Mol. Genet. 15:3459-72
171. Lin F, Morrison JM, Wu W, Worman HJ. 2005. MAN1, an integral protein of the inner nuclear membrane, binds Smad2 and Smad3 and antagonizes transforming growth factor β signaling. Hum. Mol. Genet. 14:437-45
172. Pan D, Estévez-Salmeron LD, Stroschein SL, Zhu X, He J, et al. 2005. The integral inner nuclear membrane protein MAN1 physically interacts with the R-Smad proteins to repress signaling by the transforming growth factor βsuperfamily of cytokines. J. Biol. Chem. 280:15992-6001
173. Hellemans J, Preobrazhenska O, Willaert A, Debeer P, Verdonk PC, et al. 2004. Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis. Nat. Genet. 36:1213-18
174. Huber MD, Guan T, Gerace L. 2009. Overlapping functions of nuclear envelope proteins NET25 (Lem2) and emerin in regulation of extracellular signal-regulated kinase signaling in myoblast differentiation. Mol. Cell. Biol. 29:5718-28
175. Dechat T, Vlcek S, Foisner R. 2000. Review: Lamina-associated polypeptide 2 isoforms and related proteins in cell cycle-dependent nuclear structure dynamics. J. Struct. Biol. 129:335-45
176. Dechat T, Gajewski A, Korbei B, Gerlich D, Daigle N, et al. 2004. LAP2αand BAF transiently localize to telomeres and specific regions on chromatin during nuclear assembly. J. Cell Sci. 117:6117-28
177. Dechat T, Korbei B, Vaughan OA, Vlcek S, Hutchison CJ, Foisner R. 2000. Lamina-associated polypeptide 2αbinds intranuclear A-type lamins. J. Cell Sci. 113:3473-84
178. Dorner D, Vlcek S, Foeger N, Gajewski A, Makolm C, et al. 2006. Lamina-associated polypeptide 2α regulates cell cycle progression and differentiation via the retinoblastoma-E2F pathway. J. Cell Biol. 173:83-93
179. Markiewicz E, Dechat T, Foisner R, Quinlan RA, Hutchison CJ. 2002. Lamin A/C binding protein LAP2αis required for nuclear anchorage of retinoblastoma protein. Mol. Biol. Cell 13:4401-13
180. Gotic I, Schmidt WM, Biadasiewicz K, Leschnik M, Spilka R, et al. 2010. Loss of LAP2αdelays satellite cell differentiation and affects postnatal fiber-type determination. Stem Cells 28:480-88
181. Gotic I, Leschnik M, Kolm U, Markovic M, Haubner BJ, et al. 2010. Lamina-associated polypeptide 2α loss impairs heart function and stress response in mice. Circ. Res. 106:346-53
182. Cohen TV, Gnocchi VF, Cohen JE, Phadke A, Liu H, et al. 2013. Defective skeletal muscle growth in lamin A/C-deficient mice is rescued by loss of Lap2α. Hum. Mol. Genet. 22:2852-69
183. Bertrand AT, Renou L, Papadopoulos A, Beuvin M, Lacene E, et al. 2012. DelK32-lamin A/C has abnormal location and induces incomplete tissue maturation and severe metabolic defects leading to premature death. Hum. Mol. Genet. 21:1037-48
184. Pilat U, Dechat T, Bertrand AT, Woisetschläger N, Gotic I, et al. 2013. The muscle dystrophy-causing δK32 lamin A/C mutant does not impair the functions of the nucleoplasmic lamin-A/C-LAP2αcomplex in mice. J. Cell Sci. 126:1753-62
185. Pekovic V, Harborth J, Broers JL, Ramaekers FC, van Engelen B, et al. 2007. Nucleoplasmic LAP2α-laminAcomplexes are required tomaintain a proliferative state in human fibroblasts. J. Cell Biol. 176:163-72
186. Dechat T, Gesson K, Foisner R. 2011. Lamina-independent lamins in the nuclear interior serve important functions. Cold Spring Harb. Symp. Quant. Biol. 75:533-43
187. Gesson K, Vidak S, Foisner R. 2014. Lamina-associated polypeptide (LAP)2αand nucleoplasmic lamins in adult stem cell regulation and disease. Semin. Cell Dev. Biol. 29:116-24
188. Zhang S, Schones DE, Malicet C, Rochman M, Zhou M, et al. 2013. High mobility group protein N5 (HMGN5) and lamina-associated polypeptide 2α (LAP2α) interact and reciprocally affect their genome-wide chromatin organization. J. Biol. Chem. 288:18104-9
189. Schreiber KH, Kennedy BK. 2013. When lamins go bad: nuclear structure and disease. Cell 152:1365-75
190. Worman HJ. 2012. Nuclear lamins and laminopathies. J. Pathol. 226:316-25
191. Worman HJ, Bonne G. 2007. "Laminopathies": a wide spectrum of human diseases. Exp. Cell Res. 313:2121-33
192. Bollati M, Barbiroli A, Favalli V, Arbustini E, Charron P, Bolognesi M. 2012. Structures of the lamin A/C R335W and E347K mutants: implications for dilated cardiolaminopathies. Biochem. Biophys. Res. Commun. 418:217-21
193. Bank EM, Ben-Harush K, Feinstein N, Medalia O, Gruenbaum Y. 2012. Structural and physiological phenotypes of disease-linked lamin mutations in C. Elegans. J. Struct. Biol. 177:106-12
194. Krimm I, Ostlund C, Gilquin B, Couprie J, Hossenlopp P, et al. 2002. The Ig-like structure of the Cterminal domain of lamin A/C, mutated in muscular dystrophies, cardiomyopathy, and partial lipodystrophy. Structure 10:811-23
195. Magracheva E, Kozlov S, Stewart CL, Wlodawer A, Zdanov A. 2009. Structure of the lamin A/C R482W mutant responsible for dominant familial partial lipodystrophy (FPLD). Acta Crystallogr. F 65:665-70
196. De Sandre-Giovannoli A, Bernard R, Cau P, Navarro C, Amiel J, et al. 2003. Lamin A truncation in Hutchinson-Gilford progeria. Science 300:2055
197. Eriksson M, Brown WT, Gordon LB, Glynn MW, Singer J, et al. 2003. Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature 423:293-98
198. Goldman RD, Shumaker DK, Erdos MR, Eriksson M, Goldman AE, et al. 2004. Accumulation ofmutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome. PNAS 101:8963-68
199. Fong LG, Ng JK, Meta M, Coté N, Yang SH, et al. 2004. Heterozygosity for Lmna deficiency eliminates the progeria-like phenotypes in Zmpste24-deficient mice. PNAS 101:18111-16
200. Yang SH, Chang SY, Ren S, Wang Y, Andres DA, et al. 2011. Absence of progeria-like disease phenotypes in knock-in mice expressing a non-farnesylated version of progerin. Hum. Mol. Genet. 20:436-44
201. Davies BSJ, Barnes RH, Tu Y, Ren S, Andres DA, et al. 2010. An accumulation of non-farnesylated prelamin A causes cardiomyopathy but not progeria. Hum. Mol. Genet. 19:2682-94
202. Gordon LB, Rothman FG, Lopez-Otin C, Misteli T. 2014. Progeria: a paradigm for translational medicine. Cell 156:400-7
203. Gotzmann J, Foisner R. 2005. A-type lamin complexes and regenerative potential: a step towards understanding laminopathic diseases? Histochem. Cell Biol.125:33-41
204. Gruenbaum Y, Wilson KL, Harel A, Goldberg M, Cohen M. 2000. Review: nuclear lamins-structural proteins with fundamental functions. J. Struct. Biol. 129:313-23
205. Halaschek-Wiener J, Brooks-Wilson A. 2007. Progeria of stem cells: stem cell exhaustion inHutchinson-Gilford progeria syndrome. J. Gerontol. Ser. A 62:3-8
206. Meshorer E, Gruenbaum Y. 2008. Gone with the Wnt/Notch: stem cells in laminopathies, progeria, and aging. J. Cell Biol. 181:9-13
207. Pekovic V, Hutchison CJ. 2008. Adult stem cell maintenance and tissue regeneration in the ageing context: the role for A-type lamins as intrinsic modulators of ageing in adult stem cells and their niches. J. Anat. 213:5-25
208. Goizet C, Yaou RB, Demay L, Richard P, Bouillot S, et al. 2004. A new mutation of the lamin A/C gene leading to autosomal dominant axonal neuropathy, muscular dystrophy, cardiac disease, and leuconychia. J. Med. Genet. 41:e29
209. Zhang H, Kieckhaefer JE, Cao K. 2013. Mouse models of laminopathies. Aging Cell 12:2-10
210. Banerjee A, Rathee V, Krishnaswamy R, Bhattacharjee P, Ray P, et al. 2013. Viscoelastic behavior of human lamin A proteins in the context of dilated cardiomyopathy. PLOS ONE 8:e83410
211. Dahl KN, Scaffidi P, Islam MF, Yodh AG, Wilson KL, Misteli T. 2006. Distinct structural and mechanical properties of the nuclear lamina in Hutchinson-Gilford progeria syndrome. PNAS 103:10271-76
212. Kaufmann A, Heinemann F, Radmacher M, Stick R. 2011. Amphibian oocyte nuclei expressing lamin A with the progeria mutation E145K exhibit an increased elastic modulus. Nucleus 2:310-19
213. Verstraeten VL, Ji JY, Cummings KS, Lee RT, Lammerding J. 2008. Increased mechanosensitivity and nuclear stiffness inHutchinson-Gilford progeria cells: effects of farnesyltransferase inhibitors. Aging Cell 7:383-93
214. Booth-Gauthier EA, Du V, Ghibaudo M, Rape AD, Dahl KN, Ladoux B. 2013. Hutchinson-Gilford progeria syndrome alters nuclear shape and reduces cell motility in three dimensional model substrates. Integr. Biol. 5:569-77
215. Chen ZJ, Wang WP, Chen YC, Wang JY, Lin WH, et al. 2014. Dysregulated interactions between lamin A and SUN1 induce abnormalities in the nuclear envelope and endoplasmic reticulum in progeric laminopathies. J. Cell Sci. 127:1792-804
216. Haque F, Mazzeo D, Patel JT, Smallwood DT, Ellis JA, et al. 2010. MammalianSUNprotein interaction networks at the inner nuclear membrane and their role in laminopathy disease processes. J. Biol. Chem. 285:3487-98
217. Yang L, Munck M, Swaminathan K, Kapinos LE, Noegel AA, Neumann S. 2013. Mutations in LMNA modulate the lamin A-Nesprin-2 interaction and cause LINC complex alterations. PLOS ONE 8:e71850
218. Folker ES, Ostlund C, Luxton GWG, Worman HJ, Gundersen GG. 2011. Lamin A variants that cause striated muscle disease are defective in anchoring transmembrane actin-associated nuclear lines for nuclear movement. PNAS 108:131-36
219. Bhattacharjee P, Banerjee A, Banerjee A, Dasgupta D, Sengupta K. 2013. Structural alterations of Lamin A protein in dilated cardiomyopathy. Biochemistry 52:4229-41
220. Gangemi F, Degano M. 2013. Disease-associated mutations in the coil 2B domain of human lamin A/C affect structural properties thatmediate dimerization and intermediate filament formation. J. Struct. Biol. 181:17-28
221. Qin Z, Kalinowski A, Dahl KN, Buehler MJ. 2011. Structure and stability of the lamin A tail domain and HGPS mutant. J. Struct. Biol. 175:425-33
222. Shumaker DK, Dechat T, Kohlmaier A, Adam SA, Bozovsky MR, et al. 2006. Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging. PNAS 103:8703-8
223. McCord RP, Nazario-Toole A, Zhang H, Chines PS, Zhan Y, et al. 2013. Correlated alterations in genome organization, histone methylation, and DNA-lamin A/C interactions in Hutchinson-Gilford progeria syndrome. Genome Res. 23:260-69
224. Kubben N, Adriaens M, Meuleman W, Voncken JW, van Steensel B, Misteli T. 2012. Mapping of lamin A-and progerin-interacting genome regions. Chromosoma 121:447-64
225. Heyn H, Moran S, Esteller M. 2013. AberrantDNAmethylation profiles in the premature aging disorders Hutchinson-Gilford progeria and Werner syndrome. Epigenetics 8:28-33
226. Meaburn KJ, Cabuy E, Bonne G, Levy N, Morris GE, et al. 2007. Primary laminopathy fibroblasts display altered genome organization and apoptosis. Aging Cell 6:139-53
227. Mewborn SK, Puckelwartz MJ, Abuisneineh F, Fahrenbach JP, Zhang Y, et al. 2010. Altered chromosomal positioning, compaction, and gene expression with a lamin A/C gene mutation. PLOS ONE 5:e14342
228. Mattout A, Pike BL, Towbin BD, Bank EM, Gonzalez-Sandoval A, et al. 2011. An EDMD mutation in C. Elegans lamin blocks muscle-specific gene relocation and compromises muscle integrity. Curr. Biol. 21:1603-14
229. Pegoraro G, Kubben N, Wickert U, Gohler H, Hoffmann K, Misteli T. 2009. Ageing-related chromatin defects through loss of the NURD complex. Nat. Cell Biol. 11:1261-67
230. Chapman JR, Taylor MR, Boulton SJ. 2012. Playing the end game: DNA double-strand break repair pathway choice. Mol. Cell 47:497-510
231. Liu Y, Rusinol A, Sinensky M, Wang Y, Zou Y. 2006. DNA damage responses in progeroid syndromes arise from defective maturation of prelamin A. J. Cell Sci. 119:4644-49
232. Scaffidi P, Misteli T. 2006. Lamin A-dependent nuclear defects in human aging. Science 312:1059-63
233. Liu B, Wang J, Chan KM, Tjia WM, Deng W, et al. 2005. Genomic instability in laminopathy-based premature aging. Nat. Med. 11:780-85
234. Varela I, Cadinanos J, Pendas AM, Gutierrez-Fernandez A, Folgueras AR, et al. 2005. Accelerated ageing in mice deficient in Zmpste24 protease is linked to p53 signalling activation. Nature 437:564-68
235. Liu Y, Wang Y, Rusinol AE, Sinensky MS, Liu J, et al. 2008. Involvement of xeroderma pigmentosum group A (XPA) in progeria arising from defective maturation of prelamin A. FASEB J. 22:603-11
236. Manju K, Muralikrishna B, Parnaik VK. 2006. Expression of disease-causing lamin A mutants impairs the formation of DNA repair foci. J. Cell Sci. 119:2704-14
237. Zhang H, Xiong ZM, Cao K. 2014. Mechanisms controlling the smooth muscle cell death in progeria via down-regulation of poly(ADP-ribose) polymerase 1. PNAS 111:E2261-70
238. Mahen R, Hattori H, Lee M, Sharma P, Jeyasekharan AD, Venkitaraman AR. 2013. A-type lamins maintain the positional stability of DNA damage repair foci in mammalian nuclei. PLOS ONE 8:e61893
239. Redwood AB, Perkins SM, Vanderwaal RP, Feng Z, Biehl KJ, et al. 2011. A dual role for A-type lamins in DNA double-strand break repair. Cell Cycle 10:2549-60
240. Gonzalez-Suarez I, Redwood AB, Grotsky DA, Neumann MA, Cheng EH, et al. 2011. A new pathway that regulates 53BP1 stability implicates cathepsin L and vitaminDinDNArepair. EMBO J. 30:3383-96
241. Richards SA, Muter J, Ritchie P, Lattanzi G, Hutchison CJ. 2011. The accumulation of un-repairable DNA damage in laminopathy progeria fibroblasts is caused by ROS generation and is prevented by treatment with N-acetyl cysteine. Hum. Mol. Genet. 20:3997-4004
242. Das A, Grotsky DA, Neumann MA, Kreienkamp R, Gonzalez-Suarez I, et al. 2013. Lamin A-exon9 mutation leads to telomere and chromatin defects but not genomic instability. Nucleus 4:410-19
243. De Vos WH, Houben F, Hoebe RA, Hennekam R, van Engelen B, et al. 2010. Increased plasticity of the nuclear envelope and hypermobility of telomeres due to the loss of A-type lamins. Biochim. Biophys. Acta 1800:448-58
244. Gonzalez-Suarez I, Redwood AB, Perkins SM, Vermolen B, Lichtensztejin D, et al. 2009. Novel roles for A-type lamins in telomere biology and the DNA damage response pathway. EMBO J. 28:2414-27
245. Decker ML, Chavez E, Vulto I, Lansdorp PM. 2009. Telomere length in Hutchinson-Gilford progeria syndrome. Mech. Ageing Dev. 130:377-83
246. Huang S, Risques RA, Martin GM, Rabinovitch PS, Oshima J. 2008. Accelerated telomere shortening and replicative senescence in human fibroblasts overexpressing mutant and wild-type lamin A. Exp. Cell Res. 314:82-91
247. Harborth J, Elbashir SM, Bechert K, Tuschl T, Weber K. 2001. Identification of essential genes in cultured mammalian cells using small interfering RNAs. J. Cell Sci. 114:4557-65
248. Bar DZ, Neufeld E, Feinstein N, Gruenbaum Y. 2009. Gliotoxin reverses age-dependent nuclear morphology phenotypes, ameliorates motility, but fails to affect lifespan of adult Caenorhabditis elegans. Cell Motil. Cytoskelet. 66:791-97
249. Osouda S, Nakamura Y, de Saint Phalle B, McConnell M, Horigome T, et al. 2005. Null mutants of Drosophila B-type lamin Dm0 show aberrant tissue differentiation rather than obvious nuclear shape distortion or specific defects during cell proliferation. Dev. Biol. 284:219-32
250. Vergnes L, Peterfy M, Bergo MO, Young SG, Reue K. 2004. Lamin B1 is required for mouse development and nuclear integrity. PNAS 101:10428-33
251. Coffinier C, Chang SY, Nobumori C, Tu Y, Farber EA, et al. 2010. Abnormal development of the cerebral cortex and cerebellum in the setting of lamin B2 deficiency. PNAS 107:5076-81
252. Coffinier C, Jung HJ, Nobumori C, Chang S, Tu Y, et al. 2011. Deficiencies in lamin B1 and lamin B2 cause neurodevelopmental defects and distinct nuclear shape abnormalities in neurons. Mol. Biol. Cell 22:4683-93
253. Freund A, Laberge RM, Demaria M, Campisi J. 2012. Lamin B1 loss is a senescence-associated biomarker. Mol. Biol. Cell 23:2066-75
254. Shimi T, Butin-Israeli V, Adam SA, Hamanaka RB, Goldman AE, et al. 2011. The role of nuclear lamin B1 in cell proliferation and senescence. Genes Dev. 25:2579-93
255. Barascu A, Le Chalony C, Pennarun G, Genet D, Imam N, et al. 2012. Oxidative stress induces an ATM-independent senescence pathway through p38 MAPK-mediated lamin B1 accumulation. EMBO J. 31:1080-94
256. Dreesen O, Chojnowski A, Ong PF, Zhao TY, Common JE, et al. 2013. Lamin B1 fluctuations have differential effects on cellular proliferation and senescence. J. Cell Biol. 200:605-17
257. Dreesen O, Ong PF, Chojnowski A, Colman A. 2013. The contrasting roles of lamin B1 in cellular aging and human disease. Nucleus 4:283-90
258. Hegele RA, Cao H, Liu DM, Costain GA, Charlton-Menys V, et al. 2006. Sequencing of the reannotated LMNB2 gene reveals novel mutations in patients with acquired partial lipodystrophy. Am. J. Hum. Genet. 79:383-89
259. Gao J, Li Y, Fu X, Luo X. 2012. A Chinese patient with acquired partial lipodystrophy caused by a novel mutation with LMNB2 gene. J. Pediatr. Endocrinol. Metab. 25:375-77
260. Padiath QS, Saigoh K, Schiffmann R, Asahara H, Yamada T, et al. 2006. Lamin B1 duplications cause autosomal dominant leukodystrophy. Nat. Genet. 38:1114-23
261. Potic A, Pavlovic AM, Uziel G, Kozic D, Ostojic J, et al. 2013. Adult-onset autosomal dominant leukodystrophy without early autonomic dysfunctions linked to lamin B1 duplication: a phenotypic variant. J. Neurol. 260:2124-29
262. Giorgio E, Rolyan H, Kropp L, Chakka AB, Yatsenko S, et al. 2013. Analysis of LMNB1 duplications in autosomal dominant leukodystrophy provides insights into duplication mechanisms and allele-specific expression. Hum. Mutat. 34:1160-71
263. Andres V, González JM. 2009. Role of A-type lamins in signaling, transcription, and chromatin organization. J. Cell Biol. 187:945-57
264. Heessen S, Fornerod M. 2007. The inner nuclear envelope as a transcription factor resting place. EMBO Rep. 8:914-19
265. Ozaki T, Saijo M, Murakami K, Enomoto H, Taya Y, Sakiyama S. 1994. Complex formation between lamin A and the retinoblastoma gene product: identification of the domain on lamin A required for its interaction. Oncogene 9:2649-53
266. Johnson BR, Nitta RT, Frock RL, Mounkes L, Barbie DA, et al. 2004. A-type lamins regulate retinoblastoma protein function by promoting subnuclear localization and preventing proteasomal degradation. PNAS 101:9677-82
267. Nitta RT, Jameson SA, Kudlow BA, Conlan LA, Kennedy BK. 2006. Stabilization of the retinoblastoma protein by A-type nuclear lamins is required for INK4A-mediated cell cycle arrest. Mol. Cell. Biol. 26:5360-72
268. Van Berlo JH, Voncken JW, Kubben N, Broers JL, Duisters R, et al. 2005. A-type lamins are essential for TGF-β1 induced PP2A to dephosphorylate transcription factors. Hum. Mol. Genet. 14:2839-49
269. Rodriguez J, Calvo F, González JM, Casar B, Andres V, Crespo P. 2010. ERK1/2 MAP kinases promote cell cycle entry by rapid, kinase-independent disruption of retinoblastoma-lamin A complexes. J. Cell Biol. 191:967-79
270. Bakay M, Wang Z, Melcon G, Schiltz L, Xuan J, et al. 2006. Nuclear envelope dystrophies show a transcriptional fingerprint suggesting disruption of Rb-MyoD pathways in muscle regeneration. Brain 129:996-1013
271. Marji J, O'Donoghue SI, McClintock D, Satagopam VP, Schneider R, et al. 2010. Defective lamin A-Rb signaling in Hutchinson-Gilford progeria syndrome and reversal by farnesyltransferase inhibition. PLOS ONE 5:e11132
272. Ivorra C, Kubicek M, González JM, Sanz-González SM, Alvarez-Barrientos A, et al. 2006. Amechanism of AP-1 suppression through interaction of c-Fos with lamin A/C. Genes Dev. 20:307-20
273. González JM, Navarro-Puche A, Casar B, Crespo P, Andres V. 2008. Fast regulation of AP-1 activity through interaction of lamin A/C, ERK1/2, and c-Fos at the nuclear envelope. J. Cell Biol. 183:653-66
274. Muchir A, Pavlidis P, Decostre V, Herron AJ, Arimura T, et al. 2007. Activation of MAPK pathways links LMNA mutations to cardiomyopathy in Emery-Dreifuss muscular dystrophy. J. Clin. Investig. 117:1282-93
275. Muchir A, Wu W, Choi JC, Iwata S, Morrow J, et al. 2012. Abnormal p38αmitogen-activated protein kinase signaling in dilated cardiomyopathy caused by lamin A/C gene mutation. Hum. Mol. Genet. 21:4325-33
276. Muchir A, Shan J, Bonne G, Lehnart SE, Worman HJ. 2009. Inhibition of extracellular signal-regulated kinase signaling to prevent cardiomyopathy caused by mutation in the gene encoding A-type lamins. Hum. Mol. Genet. 18:241-47
277. Wu W, Iwata S, Homma S, Worman HJ, Muchir A. 2014. Depletion of extracellular signal-regulated kinase 1 in mice with cardiomyopathy caused by lamin A/C gene mutation partially prevents pathology before isoenzyme activation. Hum. Mol. Genet. 23:1-11
278. Favreau C, Higuet D, Courvalin JC, Buendia B. 2004. Expression of a mutant lamin A that causes Emery-Dreifuss muscular dystrophy inhibits in vitro differentiation of C2C12 myoblasts. Mol. Cell. Biol. 24:1481-92
279. Frock RL, Kudlow BA, Evans AM, Jameson SA, Hauschka SD, Kennedy BK. 2006. Lamin A/C and emerin are critical for skeletal muscle satellite cell differentiation. Genes Dev. 20:486-500
280. Kandert S, Wehnert M, Muller CR, Buendia B, Dabauvalle MC. 2009. Impaired nuclear functions lead to increased senescence and inefficient differentiation in human myoblasts with a dominant p.R545C mutation in the LMNA gene. Eur. J. Cell Biol. 88:593-608
281. Boguslavsky RL, Stewart CL, Worman HJ. 2006. Nuclear lamin A inhibits adipocyte differentiation: implications for Dunnigan-type familial partial lipodystrophy. Hum. Mol. Genet. 15:653-63
282. Akter R, Rivas D, Geneau G, Drissi H, Duque G. 2009. Effect of lamin A/C knockdown on osteoblast differentiation and function. J. Bone Miner. Res. 24:283-93
283. Rauner M, Sipos W, Goettsch C, Wutzl A, Foisner R, et al. 2009. Inhibition of lamin A/C attenuates osteoblast differentiation and enhances RANKL-dependent osteoclastogenesis. J. Bone Miner. Res. 24:78-86
284. Kubben N, Voncken JW, Konings G, vanWeeghel M, van den Hoogenhof MM, et al. 2011. Post-natal myogenic and adipogenic developmental: defects and metabolic impairment upon loss of A-type lamins. Nucleus 2:195-207
285. Mateos J, De la Fuente A, Lesende-Rodriguez I, Fernandez-Pernas P, Arufe MC, Blanco FJ. 2013. Lamin A deregulation in human mesenchymal stem cells promotes an impairment in their chondrogenic potential and imbalance in their response to oxidative stress. Stem Cell Res. 11:1137-48
286. Scaffidi P, Misteli T. 2008. Lamin A-dependent misregulation of adult stem cells associated with accelerated ageing. Nat. Cell Biol. 10:452-59
287. Espada J, Varela I, Flores I, Ugalde AP, Cadinanos J, et al. 2008. Nuclear envelope defects cause stem cell dysfunction in premature-aging mice. J. Cell Biol. 181:27-35
288. Hernandez L, Roux KJ, Wong ESM, Mounkes LC, Mutalif R, et al. 2010. Functional coupling between the extracellular matrix and nuclear lamina byWnt signaling in progeria. Dev. Cell 19:413-25
289. Duband-Goulet I, Woerner S, Gasparini S, Attanda W, Kondé E, et al. 2011. Subcellular localization of SREBP1 depends on its interaction with the C-terminal region of wild-type and disease related A-type lamins. Exp. Cell Res. 317:2800-13
290. Lloyd DJ, Trembath RC, Shackleton S. 2002. A novel interaction between lamin A and SREBP1: implications for partial lipodystrophy and other laminopathies. Hum. Mol. Genet. 11:769-77
291. McKenna T, Rosengardten Y, Viceconte N, Baek JH, Grochova D, Eriksson M. 2014. Embryonic expression of the common progeroid lamin A splice mutation arrests postnatal skin development. Aging Cell 13:292-302
292. Osorio FG, Barcena C, Soria-Valles C, Ramsay AJ, de Carlos F, et al. 2012. Nuclear lamina defects cause ATM-dependentNF-κB activation and link accelerated aging to a systemic inflammatory response. Genes Dev. 26:2311-24
293. Ramos FJ, Chen SC, Garelick MG, Dai DF, Liao CY, et al. 2012. Rapamycin reverses elevatedmTORC1 signaling in lamin A/C-deficient mice, rescues cardiac and skeletalmuscle function, and extends survival. Sci. Transl. Med. 4:144ra03
294. Ramos FJ, Kaeberlein M, Kennedy BK. 2013. Elevated MTORC1 signaling and impaired autophagy. Autophagy 9:108-9
295. Cao K, Graziotto JJ, Blair CD, Mazzulli JR, Erdos MR, et al. 2011. Rapamycin reverses cellular phenotypes and enhances mutant protein clearance in Hutchinson-Gilford progeria syndrome cells. Sci. Transl. Med. 3:89ra58
296. Rosengardten Y, McKenna T, Grochova D, Eriksson M. 2011. Stem cell depletion in Hutchinson-Gilford progeria syndrome. Aging Cell 10:1011-20
297. Bridger JM, Kill IR. 2004. Aging of Hutchinson-Gilford progeria syndrome fibroblasts is characterised by hyperproliferation and increased apoptosis. Exp. Gerontol. 39:717-24
298. Mounkes LC, Kozlov S, Hernandez L, Sullivan T, Stewart CL. 2003. A progeroid syndrome in mice is caused by defects in A-type lamins. Nature 423:298-301
299. Liu B, Ghosh S, Yang X, Zheng H, Liu X, et al. 2012. Resveratrol rescues SIRT1-dependent adult stem cell decline and alleviates progeroid features in laminopathy-based progeria. Cell Metab. 16:738-50
300. Liu G-H, Barkho BZ, Ruiz S, Diep D, Qu J, et al. 2011. Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome. Nature 472:221-25
301. Zhang J, Lian Q, Zhu G, Zhou F, Sui L, et al. 2011. A human iPSC model of Hutchinson Gilford progeria reveals vascular smooth muscle and mesenchymal stem cell defects. Cell Stem Cell 8:31-45
302. Varga R, Eriksson M, Erdos MR, Olive M, Harten I, et al. 2006. Progressive vascular smooth muscle cell defects in a mouse model of Hutchinson-Gilford progeria syndrome. PNAS 103:3250-55
303. Liu Y, Drozdov I, Shroff R, Beltran LE, Shanahan CM. 2013. PrelaminAaccelerates vascular calcification via activation of the DNA damage response and senescence-associated secretory phenotype in vascular smooth muscle cells. Circ. Res. 112:e99-109
304. Chen CY, Chi YH, Mutalif RA, Starost MF, Myers TG, et al. 2012. Accumulation of the inner nuclear envelope protein Sun1 is pathogenic in progeric and dystrophic laminopathies. Cell 149:565-77
305. Cattin ME, Bertrand AT, Schlossarek S, Le Bihan MC, Skov Jensen S, et al. 2013. Heterozygous LmnadelK32 mice develop dilated cardiomyopathy through a combined pathomechanism of haploinsufficiency and peptide toxicity. Hum. Mol. Genet. 22:3152-64
306. de la Rosa J, Freije JM, Cabanillas R, Osorio FG, Fraga MF, et al. 2013. Prelamin A causes progeria through cell-extrinsic mechanisms and prevents cancer invasion. Nat. Commun. 4:2268
307. Hegele RA, Anderson CM, Wang J, Jones DC, Cao H. 2000. Association between nuclear lamin A/C R482Q mutation and partial lipodystrophy with hyperinsulinemia, dyslipidemia, hypertension, and diabetes. Genome Res. 10:652-58
308. Shimobayashi M, Hall MN. 2014. Making new contacts: the mTOR network in metabolism and signalling crosstalk. Nat. Rev. Mol. Cell Biol. 15:155-62
309. Choi JC, Worman HJ. 2013. Reactivation of autophagy ameliorates LMNA cardiomyopathy. Autophagy 9:110-11
310. Lopez-Mejia IC, de Toledo M, Chavey C, Lapasset L, Cavelier P, et al. 2014. Antagonistic functions of LMNA isoforms in energy expenditure and lifespan. EMBO Rep. 15:529-39