DNA methylation and the functional organization of the nuclear compartment

Seminars in Cell and Developmental Biology

Volumn 21, Issue 2, 2010, Pages 238-246

  Espada, Jesús ^a   Esteller, Manel ^b,c  

^a UNIVERSIDAD AUTÓNOMA DE MADRID   (Spain)

^b INSTITUCIÓ CATALANA DE RECERCA I ESTUDIS AVANÇATS ICREA   (Spain)

^c BELLVITGE BIOMEDICAL RESEARCH INSTITUTE IDIBELL   (Spain)

Author keywords

DNA methylation; DNA methyltransferases; Nuclear architecture; Nuclear organization

Indexed keywords

DNA METHYLTRANSFERASE;

CELL NUCLEUS; DNA METHYLATION; HUMAN; REVIEW; TRANSCRIPTION REGULATION;

EID: 77049111268     PISSN: 10849521     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.semcdb.2009.10.006     Document Type: Review

References (123)

1. Waddington C.H. The nucleolus-retrospect and prospect. Natl Cancer Inst Monogr 23 (1966) 563-572
2. Holliday R. DNA methylation and epigenetic mechanisms. Cell Biophys 15 (1989) 15-20
3. Goldberg A.D., Allis C.D., and Bernstein E. Epigenetics: a landscape takes shape. Cell 128 (2007) 635-638
4. Dodge J.E., Ramsahoye B.H., Wo Z.G., Okano M., and Li E. De novo methylation of MMLV provirus in embryonic stem cells: CpG versus non-CpG methylation. Gene 289 (2002) 41-48
5. Haines T.R., Rodenhiser D.I., and Ainsworth P.J. Allele-specific non-CpG methylation of the Nf1 gene during early mouse development. Dev Biol 240 (2001) 585-598
6. Vinogradov A.E. Measurement by flow cytometry of genomic AT/GC ratio and genome size. Cytometry 16 (1994) 34-40
7. Aissani B., and Bernardi G. CpG islands, genes and isochores in the genomes of vertebrates. Gene 106 (1991) 185-195
8. Aissani B., and Bernardi G. CpG islands: features and distribution in the genomes of vertebrates. Gene 106 (1991) 173-183
9. Tucker K.L. Methylated cytosine and the brain: a new base for neuroscience. Neuron 30 (2001) 649-652
10. Jabbari K., and Bernardi G. Cytosine methylation and CpG, TpG (CpA) and TpA frequencies. Gene 333 (2004) 143-149
11. Clark S.J., Harrison J., Paul C.L., and Frommer M. High sensitivity mapping of methylated cytosines. Nucleic Acids Res 22 (1994) 2990-2997
12. Yoder J.A., Soman N.S., Verdine G.L., and Bestor T.H. DNA (cytosine-5)-methyltransferases in mouse cells and tissues. Studies with a mechanism-based probe. J Mol Biol 270 (1997) 385-395
13. Yoder J.A., Walsh C.P., and Bestor T.H. Cytosine methylation and the ecology of intragenomic parasites. Trends Genet 13 (1997) 335-340
14. Takai D., and Jones P.A. Comprehensive analysis of CpG islands in human chromosomes 21 and 22. Proc Natl Acad Sci USA 99 (2002) 3740-3745
15. Miranda T.B., and Jones P.A. DNA methylation: the nuts and bolts of repression. J Cell Physiol 213 (2007) 384-390
16. Jones P.A., and Baylin S.B. The fundamental role of epigenetic events in cancer. Nat Rev Genet 3 (2002) 415-428
17. Jaenisch R., and Bird A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet 33 Suppl. (2003) 245-254
18. Reik W., Dean W., and Walter J. Epigenetic reprogramming in mammalian development. Science 293 (2001) 1089-1093
19. Jackson-Grusby L., Beard C., Possemato R., Tudor M., Fambrough D., Csankovszki G., et al. Loss of genomic methylation causes p53-dependent apoptosis and epigenetic deregulation. Nat Genet 27 (2001) 31-39
20. Okano M., Bell D.W., Haber D.A., and Li E. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99 (1999) 247-257
21. Li E., Bestor T.H., and Jaenisch R. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69 (1992) 915-926
22. Chen T., Hevi S., Gay F., Tsujimoto N., He T., Zhang B., et al. Complete inactivation of DNMT1 leads to mitotic catastrophe in human cancer cells. Nat Genet 39 (2007) 391-396
23. Stancheva I., El-Maarri O., Walter J., Niveleau A., and Meehan R.R. DNA methylation at promoter regions regulates the timing of gene activation in Xenopus laevis embryos. Dev Biol 243 (2002) 155-165
24. Stancheva I., and Meehan R.R. Transient depletion of xDnmt1 leads to premature gene activation in Xenopus embryos. Genes Dev 14 (2000) 313-327
25. Esteller M. Epigenetics in cancer. N Engl J Med 358 (2008) 1148-1159
26. Bestor T.H. The DNA methyltransferases of mammals. Hum Mol Genet 9 (2000) 2395-2402
27. Robertson K.D. DNA methylation and chromatin-unraveling the tangled web. Oncogene 21 (2002) 5361-5379
28. Leonhardt H., Page A.W., Weier H.U., and Bestor T.H. A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei. Cell 71 (1992) 865-873
29. Chuang L.S., Ian H.I., Koh T.W., Ng H.H., Xu G., and Li B.F. Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1. Science 277 (1997) 1996-2000
30. Yokochi T., and Robertson K.D. Preferential methylation of unmethylated DNA by Mammalian de novo DNA methyltransferase Dnmt3a. J Biol Chem 277 (2002) 11735-11745
31. Rhee I., Jair K.W., Yen R.W., Lengauer C., Herman J.G., Kinzler K.W., et al. CpG methylation is maintained in human cancer cells lacking DNMT1. Nature 404 (2000) 1003-1007
32. Rhee I., Bachman K.E., Park B.H., Jair K.W., Yen R.W., Schuebel K.E., et al. DNMT1 and DNMT3b cooperate to silence genes in human cancer cells. Nature 416 (2002) 552-556
33. Kim G.D., Ni J., Kelesoglu N., Roberts R.J., and Pradhan S. Co-operation and communication between the human maintenance and de novo DNA (cytosine-5) methyltransferases. EMBO J 21 (2002) 4183-4195
34. Okano M., Xie S., and Li E. Dnmt2 is not required for de novo and maintenance methylation of viral DNA in embryonic stem cells. Nucleic Acids Res 26 (1998) 2536-2540
35. Yoder J.A., and Bestor T.H. A candidate mammalian DNA methyltransferase related to pmt1p of fission yeast. Hum Mol Genet 7 (1998) 279-284
36. Hermann A., Schmitt S., and Jeltsch A. The human Dnmt2 has residual DNA-(cytosine-C5) methyltransferase activity. J Biol Chem 278 (2003) 31717-31721
37. Hata K., Kusumi M., Yokomine T., Li E., and Sasaki H. Meiotic and epigenetic aberrations in Dnmt3L-deficient male germ cells. Mol Reprod Dev 73 (2006) 116-122
38. Gilbert N., Gilchrist S., and Bickmore W.A. Chromatin organization in the mammalian nucleus. Int Rev Cytol 242 (2005) 283-336
39. Zlatanova J., Seebart C., and Tomschik M. The linker-protein network: control of nucleosomal DNA accessibility. Trends Biochem Sci 33 (2008) 247-253
40. Saha A., Wittmeyer J., and Cairns B.R. Chromatin remodelling: the industrial revolution of DNA around histones. Nat Rev Mol Cell Biol 7 (2006) 437-447
41. Bird A.P., and Wolffe A.P. Methylation-induced repression-belts, braces, and chromatin. Cell 99 (1999) 451-454
42. Klose R.J., and Bird A.P. Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci 31 (2006) 89-97
43. Buschhausen G., Wittig B., Graessmann M., and Graessmann A. Chromatin structure is required to block transcription of the methylated herpes simplex virus thymidine kinase gene. Proc Natl Acad Sci USA 84 (1987) 1177-1181
44. Kass S.U., Landsberger N., and Wolffe A.P. DNA methylation directs a time-dependent repression of transcription initiation. Curr Biol 7 (1997) 157-165
45. Campanero M.R., Armstrong M.I., and Flemington E.K. CpG methylation as a mechanism for the regulation of E2F activity. Proc Natl Acad Sci USA 97 (2000) 6481-6486
46. Prendergast G.C., and Ziff E.B. Methylation-sensitive sequence-specific DNA binding by the c-Myc basic region. Science 251 (1991) 186-189
47. Iguchi-Ariga S.M., and Schaffner W. CpG methylation of the cAMP-responsive enhancer/promoter sequence TGACGTCA abolishes specific factor binding as well as transcriptional activation. Genes Dev 3 (1989) 612-619
48. Kass S.U., Pruss D., and Wolffe A.P. How does DNA methylation repress transcription?. Trends Genet 13 (1997) 444-449
49. Clouaire T., and Stancheva I. Methyl-CpG binding proteins: specialized transcriptional repressors or structural components of chromatin?. Cell Mol Life Sci 65 (2008) 1509-1522
50. Misteli T. Beyond the sequence: cellular organization of genome function. Cell 128 (2007) 787-800
51. Misteli T. Concepts in nuclear architecture. Bioessays 27 (2005) 477-487
52. Taddei A., Hediger F., Neumann F.R., and Gasser S.M. The function of nuclear architecture: a genetic approach. Annu Rev Genet 38 (2004) 305-345
53. Cremer T., and Cremer C. Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nat Rev Genet 2 (2001) 292-301
54. Carmo-Fonseca M. The contribution of nuclear compartmentalization to gene regulation. Cell 108 (2002) 513-521
55. Carmo-Fonseca M., Mendes-Soares L., and Campos I. To be or not to be in the nucleolus. Nat Cell Biol 2 (2000) E107-112
56. Olson M.O., Dundr M., and Szebeni A. The nucleolus: an old factory with unexpected capabilities. Trends Cell Biol 10 (2000) 189-196
57. Tao W., and Levine A.J. P19(ARF) stabilizes p53 by blocking nucleo-cytoplasmic shuttling of Mdm2. Proc Natl Acad Sci USA 96 (1999) 6937-6941
58. Matera A.G. Nuclear bodies: multifaceted subdomains of the interchromatin space. Trends Cell Biol 9 (1999) 302-309
59. Cioce M., and Lamond A.I. Cajal bodies: a long history of discovery. Annu Rev Cell Dev Biol 21 (2005) 105-131
60. Hebert M.D., Szymczyk P.W., Shpargel K.B., and Matera A.G. Coilin forms the bridge between Cajal bodies and SMN, the spinal muscular atrophy protein. Genes Dev 15 (2001) 2720-2729
61. Zhu Y., Tomlinson R.L., Lukowiak A.A., Terns R.M., and Terns M.P. Telomerase RNA accumulates in Cajal bodies in human cancer cells. Mol Biol Cell 15 (2004) 81-90
62. Jady B.E., Bertrand E., and Kiss T. Human telomerase RNA and box H/ACA scaRNAs share a common Cajal body-specific localization signal. J Cell Biol 164 (2004) 647-652
63. Bernardi R., and Pandolfi P.P. Structure, dynamics and functions of promyelocytic leukaemia nuclear bodies. Nat Rev Mol Cell Biol 8 (2007) 1006-1016
64. Lamond A.I., and Spector D.L. Nuclear speckles: a model for nuclear organelles. Nat Rev Mol Cell Biol 4 (2003) 605-612
65. Iborra F.J., Jackson D.A., and Cook P.R. Coupled transcription and translation within nuclei of mammalian cells. Science 293 (2001) 1139-1142
66. Iborra F.J., Pombo A., Jackson D.A., and Cook P.R. Active RNA polymerases are localized within discrete transcription "factories" in human nuclei. J Cell Sci 109 Pt 6 (1996) 1427-1436
67. Jackson D.A., Iborra F.J., Manders E.M., and Cook P.R. Numbers and organization of RNA polymerases, nascent transcripts, and transcription units in HeLa nuclei. Mol Biol Cell 9 (1998) 1523-1536
68. Hochstrasser M., Mathog D., Gruenbaum Y., Saumweber H., and Sedat J.W. Spatial organization of chromosomes in the salivary gland nuclei of Drosophila melanogaster. J Cell Biol 102 (1986) 112-123
69. Hiraoka Y., Agard D.A., and Sedat J.W. Temporal and spatial coordination of chromosome movement, spindle formation, and nuclear envelope breakdown during prometaphase in Drosophila melanogaster embryos. J Cell Biol 111 (1990) 2815-2828
70. Croft J.A., Bridger J.M., Boyle S., Perry P., Teague P., and Bickmore W.A. Differences in the localization and morphology of chromosomes in the human nucleus. J Cell Biol 145 (1999) 1119-1131
71. Bridger J.M., Boyle S., Kill I.R., and Bickmore W.A. Re-modelling of nuclear architecture in quiescent and senescent human fibroblasts. Curr Biol 10 (2000) 149-152
72. Boyle S., Gilchrist S., Bridger J.M., Mahy N.L., Ellis J.A., and Bickmore W.A. The spatial organization of human chromosomes within the nuclei of normal and emerin-mutant cells. Hum Mol Genet 10 (2001) 211-219
73. Tanabe H., Muller S., Neusser M., von Hase J., Calcagno E., Cremer M., et al. Evolutionary conservation of chromosome territory arrangements in cell nuclei from higher primates. Proc Natl Acad Sci USA 99 (2002) 4424-4429
74. Cremer M., Kupper K., Wagler B., Wizelman L., von Hase J., Weiland Y., et al. Inheritance of gene density-related higher order chromatin arrangements in normal and tumor cell nuclei. J Cell Biol 162 (2003) 809-820
75. Gilbert N., Boyle S., Fiegler H., Woodfine K., Carter N.P., and Bickmore W.A. Chromatin architecture of the human genome: gene-rich domains are enriched in open chromatin fibers. Cell 118 (2004) 555-566
76. Sun H.B., Shen J., and Yokota H. Size-dependent positioning of human chromosomes in interphase nuclei. Biophys J 79 (2000) 184-190
77. Sun H.B., and Yokota H. Correlated positioning of homologous chromosomes in daughter fibroblast cells. Chromosome Res 7 (1999) 603-610
78. Bolzer A., Kreth G., Solovei I., Koehler D., Saracoglu K., Fauth C., et al. Three-dimensional maps of all chromosomes in human male fibroblast nuclei and prometaphase rosettes. PLoS Biol 3 (2005) e157
79. Parada L.A., McQueen P.G., Munson P.J., and Misteli T. Conservation of relative chromosome positioning in normal and cancer cells. Curr Biol 12 (2002) 1692-1697
80. Shopland L.S., Byron M., Stein J.L., Lian J.B., Stein G.S., and Lawrence J.B. Replication-dependent histone gene expression is related to Cajal body (CB) association but does not require sustained CB contact. Mol Biol Cell 12 (2001) 565-576
81. Wang J., Shiels C., Sasieni P., Wu P.J., Islam S.A., Freemont P.S., et al. Promyelocytic leukemia nuclear bodies associate with transcriptionally active genomic regions. J Cell Biol 164 (2004) 515-526
82. Shopland L.S., Johnson C.V., Byron M., McNeil J., and Lawrence J.B. Clustering of multiple specific genes and gene-rich R-bands around SC-35 domains: evidence for local euchromatic neighborhoods. J Cell Biol 162 (2003) 981-990
83. Schul W., van Driel R., and de Jong L. Coiled bodies and U2 snRNA genes adjacent to coiled bodies are enriched in factors required for snRNA transcription. Mol Biol Cell 9 (1998) 1025-1036
84. Frey M.R., and Matera A.G. RNA-mediated interaction of Cajal bodies and U2 snRNA genes. J Cell Biol 154 (2001) 499-509
85. Hernandez-Verdun D., Roussel P., and Gebrane-Younes J. Emerging concepts of nucleolar assembly. J Cell Sci 115 (2002) 2265-2270
86. Cremer T., Cremer M., Dietzel S., Muller S., Solovei I., and Fakan S. Chromosome territories-a functional nuclear landscape. Curr Opin Cell Biol 18 (2006) 307-316
87. Walter J., Schermelleh L., Cremer M., Tashiro S., and Cremer T. Chromosome order in HeLa cells changes during mitosis and early G1, but is stably maintained during subsequent interphase stages. J Cell Biol 160 (2003) 685-697
88. Thomson I., Gilchrist S., Bickmore W.A., and Chubb J.R. The radial positioning of chromatin is not inherited through mitosis but is established de novo in early G1. Curr Biol 14 (2004) 166-172
89. Parada L.A., McQueen P.G., and Misteli T. Tissue-specific spatial organization of genomes. Genome Biol 5 (2004) R44
90. Chakalova L., Debrand E., Mitchell J.A., Osborne C.S., and Fraser P. Replication and transcription: shaping the landscape of the genome. Nat Rev Genet 6 (2005) 669-677
91. Fraser P., and Bickmore W. Nuclear organization of the genome and the potential for gene regulation. Nature 447 (2007) 413-417
92. Marenduzzo D., Micheletti C., and Cook P.R. Entropy-driven genome organization. Biophys J 90 (2006) 3712-3721
93. Barbin A., Montpellier C., Kokalj-Vokac N., Gibaud A., Niveleau A., Malfoy B., et al. New sites of methylcytosine-rich DNA detected on metaphase chromosomes. Hum Genet 94 (1994) 684-692
94. Espada J., Ballestar E., Fraga M.F., Villar-Garea A., Juarranz A., Stockert J.C., et al. Human DNA methyltransferase 1 is required for maintenance of the histone H3 modification pattern. J Biol Chem 279 (2004) 37175-37184
95. Espada J., Varela I., Flores I., Ugalde A.P., Cadinanos J., Pendas A.M., et al. Nuclear envelope defects cause stem cell dysfunction in premature-aging mice. J Cell Biol 181 (2008) 27-35
96. de Capoa A., Menendez F., Poggesi I., Giancotti P., Grappelli C., Marotta M.R., et al. Cytological evidence for 5-azacytidine-induced demethylation of the heterochromatic regions of human chromosomes. Chromosome Res 4 (1996) 271-276
97. Kosak S.T., and Groudine M. Form follows function: the genomic organization of cellular differentiation. Genes Dev 18 (2004) 1371-1384
98. Zink D., Fischer A.H., and Nickerson J.A. Nuclear structure in cancer cells. Nat Rev Cancer 4 (2004) 677-687
99. Burke B., and Stewart C.L. Life at the edge: the nuclear envelope and human disease. Nat Rev Mol Cell Biol 3 (2002) 575-585
100. Francastel C., Schubeler D., Martin D.I., and Groudine M. Nuclear compartmentalization and gene activity. Nat Rev Mol Cell Biol 1 (2000) 137-143
101. Foster H.A., and Bridger J.M. The genome and the nucleus: a marriage made by evolution. Genome organisation and nuclear architecture. Chromosoma 114 (2005) 212-229
102. Santos A.P., Abranches R., Stoger E., Beven A., Viegas W., and Shaw P.J. The architecture of interphase chromosomes and gene positioning are altered by changes in DNA methylation and histone acetylation. J Cell Sci 115 (2002) 4597-4605
103. Schmid M., Haaf T., and Grunert D. 5-Azacytidine-induced undercondensations in human chromosomes. Hum Genet 67 (1984) 257-263
104. Ma Y., Jacobs S.B., Jackson-Grusby L., Mastrangelo M.A., Torres-Betancourt J.A., Jaenisch R., et al. DNA CpG hypomethylation induces heterochromatin reorganization involving the histone variant macroH2A. J Cell Sci 118 (2005) 1607-1616
105. Rougier N., Bourc'his D., Gomes D.M., Niveleau A., Plachot M., Paldi A., et al. Chromosome methylation patterns during mammalian preimplantation development. Genes Dev 12 (1998) 2108-2113
106. Coffigny H., Bourgeois C., Ricoul M., Bernardino J., Vilain A., Niveleau A., et al. Alterations of DNA methylation patterns in germ cells and Sertoli cells from developing mouse testis. Cytogenet Cell Genet 87 (1999) 175-181
107. Russo V., Martelli A., Berardinelli P., Di Giacinto O., Bernabo N., Fantasia D., et al. Modifications in chromatin morphology and organization during sheep oogenesis. Microsc Res Tech 70 (2007) 733-744
108. Hajkova P., Ancelin K., Waldmann T., Lacoste N., Lange U.C., Cesari F., et al. Chromatin dynamics during epigenetic reprogramming in the mouse germ line. Nature 452 (2008) 877-881
109. Bitonti M.B., Cozza R., Chiappetta A., Giannino D., Ruffini Castiglione M., Dewitte W., et al. Distinct nuclear organization, DNA methylation pattern and cytokinin distribution mark juvenile, juvenile-like and adult vegetative apical meristems in peach (Prunus persica (L.) Batsch). J Exp Bot 53 (2002) 1047-1054
110. Kobayakawa S., Miike K., Nakao M., and Abe K. Dynamic changes in the epigenomic state and nuclear organization of differentiating mouse embryonic stem cells. Genes Cells 12 (2007) 447-460
111. Bibikova M., Laurent L.C., Ren B., Loring J.F., and Fan J.B. Unraveling epigenetic regulation in embryonic stem cells. Cell Stem Cell 2 (2008) 123-134
112. Bibikova M., Chudin E., Wu B., Zhou L., Garcia E.W., Liu Y., et al. Human embryonic stem cells have a unique epigenetic signature. Genome Res 16 (2006) 1075-1083
113. Tessadori F., Chupeau M.C., Chupeau Y., Knip M., Germann S., van Driel R., et al. Large-scale dissociation and sequential reassembly of pericentric heterochromatin in dedifferentiated Arabidopsis cells. J Cell Sci 120 (2007) 1200-1208
114. Tariq M., Saze H., Probst A.V., Lichota J., Habu Y., and Paszkowski J. Erasure of CpG methylation in Arabidopsis alters patterns of histone H3 methylation in heterochromatin. Proc Natl Acad Sci USA 100 (2003) 8823-8827
115. Ramirez C.L., Cadinanos J., Varela I., Freije J.M., and Lopez-Otin C. Human progeroid syndromes, aging and cancer: new genetic and epigenetic insights into old questions. Cell Mol Life Sci 64 (2007) 155-170
116. Xu G.L., Bestor T.H., Bourc'his D., Hsieh C.L., Tommerup N., Bugge M., et al. Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene. Nature 402 (1999) 187-191
117. Brown D.C., Grace E., Sumner A.T., Edmunds A.T., and Ellis P.M. ICF syndrome (immunodeficiency, centromeric instability and facial anomalies): investigation of heterochromatin abnormalities and review of clinical outcome. Hum Genet 96 (1995) 411-416
118. Gisselsson D., Shao C., Tuck-Muller C.M., Sogorovic S., Palsson E., Smeets D., et al. Interphase chromosomal abnormalities and mitotic missegregation of hypomethylated sequences in ICF syndrome cells. Chromosoma 114 (2005) 118-126
119. Matarazzo M.R., Boyle S., D'Esposito M., and Bickmore W.A. Chromosome territory reorganization in a human disease with altered DNA methylation. Proc Natl Acad Sci USA 104 (2007) 16546-16551
120. Egger G., Jeong S., Escobar S.G., Cortez C.C., Li T.W., Saito Y., et al. Identification of DNMT1 (DNA methyltransferase 1) hypomorphs in somatic knockouts suggests an essential role for DNMT1 in cell survival. Proc Natl Acad Sci USA 103 (2006) 14080-14085
121. Spada F., Haemmer A., Kuch D., Rothbauer U., Schermelleh L., Kremmer E., et al. DNMT1 but not its interaction with the replication machinery is required for maintenance of DNA methylation in human cells. J Cell Biol 176 (2007) 565-571
122. Espada J., Ballestar E., Santoro R., Fraga M.F., Villar-Garea A., Nemeth A., et al. Epigenetic disruption of ribosomal RNA genes and nucleolar architecture in DNA methyltransferase 1 (Dnmt1) deficient cells. Nucleic Acids Res 35 (2007) 2191-2198
123. Gilbert N., Thomson I., Boyle S., Allan J., Ramsahoye B., and Bickmore W.A. DNA methylation affects nuclear organization, histone modifications, and linker histone binding but not chromatin compaction. J Cell Biol 177 (2007) 401-411