Gene regulation and epigenetics in Friedreich's ataxia

Journal of Neurochemistry

Volumn 126, Issue SUPPL.1, 2013, Pages 21-42

  Yandim, Cihangir ^a   Natisvili, Theona ^a   Festenstein, Richard ^a  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

epigenetics; Frataxin; Friedreich's ataxia; FXN; GAA; heterochromatin

Indexed keywords

ADENINE; COMPLEMENTARY RNA; DNA METHYLTRANSFERASE; EARLY GROWTH RESPONSE FACTOR 3; FRATAXIN; GUANINE; HISTONE; HISTONE DEACETYLASE INHIBITOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; REACTIVE OXYGEN METABOLITE; TATA BINDING PROTEIN; TRANSCRIPTION FACTOR AP 2; TRANSCRIPTION FACTOR CTCF;

DNA CONFORMATION; DNA FLANKING REGION; DNA METHYLATION; DNA SEQUENCE; EPIGENETICS; FRIEDREICH ATAXIA; FXN GENE; GENE; GENE EXPRESSION REGULATION; GENE LOCUS; GENE SILENCING; HETEROCHROMATIN; HISTONE MODIFICATION; HUMAN; INTRON; MITOCHONDRIAL RESPIRATION; MOLECULAR PATHOLOGY; NONHUMAN; PRIORITY JOURNAL; PROMOTER REGION; REVIEW; RNA TRANSLATION; TRANSCRIPTION INITIATION SITE; TRANSCRIPTION REGULATION; TRINUCLEOTIDE REPEAT;

EPIGENETICS; FRATAXIN; FRIEDREICH'S ATAXIA; FXN; GAA; HETEROCHROMATIN;

DNA METHYLATION; DNA REPEAT EXPANSION; DNA, ANTISENSE; EPIGENESIS, GENETIC; FRIEDREICH ATAXIA; GENE EXPRESSION REGULATION; HISTONES; HUMANS; IRON-BINDING PROTEINS; RNA INTERFERENCE; TRANSCRIPTION, GENETIC;

EID: 84880386750     PISSN: 00223042     EISSN: 14714159     Source Type: Journal    
DOI: 10.1111/jnc.12254     Document Type: Review

References (245)

1. Aagaard L., Laible G., Selenko P., et al,. (1999) Functional mammalian homologues of the Drosophila PEV-modifier Su(var)3-9 encode centromere- associated proteins which complex with the heterochromatin component M31. EMBO J. 18, 1923-1938.
2. Allan J., Hartman P. G., Crane-Robinson C., and, Aviles F. X., (1980) The structure of histone H1 and its location in chromatin. Nature 288, 675-679.
3. Allfrey V. G., Faulkner R., and, Mirsky A. E., (1964) Acetylation and Methylation of Histones and Their Possible Role in the Regulation of Rna Synthesis. Proc. Natl Acad. Sci. USA 51, 786-794.
4. Al-Mahdawi S., Pinto R. M., Ruddle P., Carroll C., Webster Z., and, Pook M., (2004) GAA repeat instability in Friedreich ataxia YAC transgenic mice. Genomics 84, 301-310.
5. Al-Mahdawi S., Pinto R. M., Varshney D., et al,. (2006) GAA repeat expansion mutation mouse models of Friedreich ataxia exhibit oxidative stress leading to progressive neuronal and cardiac pathology. Genomics 88, 580-590.
6. Al-Mahdawi S., Pinto R. M., Ismail O., Varshney D., Lymperi S., Sandi C., Trabzuni D., and, Pook M., (2008) The Friedreich ataxia GAA repeat expansion mutation induces comparable epigenetic changes in human and transgenic mouse brain and heart tissues. Hum. Mol. Genet. 17, 735-746.
7. Athanikar J. N., Badge R. M., and, Moran J. V., (2004) A YY1-binding site is required for accurate human LINE-1 transcription initiation. Nucleic Acids Res. 32, 3846-3855.
8. Ayoub N., Jeyasekharan A. D., Bernal J. A., and, Venkitaraman A. R., (2008) HP1-beta mobilization promotes chromatin changes that initiate the DNA damage response. Nature 453, 682-686.
9. Balakrishnan L., and, Milavetz B., (2010) Decoding the histone H4 lysine 20 methylation mark. Crit. Rev. Biochem. Mol. Biol. 45, 440-452.
10. Bannister A. J., and, Kouzarides T., (2011) Regulation of chromatin by histone modifications. Cell Res. 21, 381-395.
11. Bannister A. J., Zegerman P., Partridge J. F., Miska E. A., Thomas J. O., Allshire R. C., and, Kouzarides T., (2001) Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature 410, 120-124.
12. Baralle M., Pastor T., Bussani E., and, Pagani F., (2008) Influence of Friedreich ataxia GAA noncoding repeat expansions on pre-mRNA processing. Am. J. Hum. Genet. 83, 77-88.
13. Barski A., Cuddapah S., Cui K., Roh T. Y., Schones D. E., Wang Z., Wei G., Chepelev I., and, Zhao K., (2007) High-resolution profiling of histone methylations in the human genome. Cell 129, 823-837.
14. Bartkuhn M., Straub T., Herold M., Herrmann M., Rathke C., Saumweber H., Gilfillan G. D., Becker P. B., and, Renkawitz R., (2009) Active promoters and insulators are marked by the centrosomal protein 190. EMBO J. 28, 877-888.
15. Bashkirov V. N., (2002) The origin of heterochromatin in eukaryotes. Genetika 38, 789-792.
16. Beard C., Li E., and, Jaenisch R., (1995) Loss of methylation activates Xist in somatic but not in embryonic cells. Genes Dev. 9, 2325-2334.
17. Beisel C., and, Paro R., (2011) Silencing chromatin: comparing modes and mechanisms. Nat. Rev. Genet. 12, 123-135.
18. Belancio V. P., Hedges D. J., and, Deininger P., (2008) Mammalian non-LTR retrotransposons: for better or worse, in sickness and in health. Genome Res. 18, 343-358.
19. Bentin T., Cherny D., Larsen H. J., and, Nielsen P. E., (2005) Transcription arrest caused by long nascent RNA chains. Biochim. Biophys. Acta 1727, 97-105.
20. Bernstein E., Kim S. Y., Carmell M. A., Murchison E. P., Alcorn H., Li M. Z., Mills A. A., Elledge S. J., Anderson K. V., and, Hannon G. J., (2003) Dicer is essential for mouse development. Nat. Genet. 35, 215-217.
21. Bestor T. H., and, Ingram V. M., (1983) Two DNA methyltransferases from murine erythroleukemia cells: purification, sequence specificity, and mode of interaction with DNA. Proc. Natl Acad. Sci. USA 80, 5559-5563.
22. Bhidayasiri R., Perlman S. L., Pulst S. M., and, Geschwind D. H., (2005) Late-onset Friedreich ataxia: phenotypic analysis, magnetic resonance imaging findings, and review of the literature. Arch. Neurol. 62, 1865-1869.
23. Bidichandani S. I., Ashizawa T., and, Patel P. I., (1998) The GAA triplet-repeat expansion in Friedreich ataxia interferes with transcription and may be associated with an unusual DNA structure. Am. J. Hum. Genet. 62, 111-121.
24. Boehm T., Scheiber-Mojdehkar B., Kluge B., Goldenberg H., Laccone F., and, Sturm B., (2011) Variations of frataxin protein levels in normal individuals. Neurol. Sci. 32, 327-330.
25. Bolland D. J., Wood A. L., Johnston C. M., Bunting S. F., Morgan G., Chakalova L., Fraser P. J., and, Corcoran A. E., (2004) Antisense intergenic transcription in V(D)J recombination. Nat. Immunol. 5, 630-637.
26. Bolland D. J., Wood A. L., Afshar R., Featherstone K., Oltz E. M., and, Corcoran A. E., (2007) Antisense intergenic transcription precedes Igh D-to-J recombination and is controlled by the intronic enhancer Emu. Mol. Cell. Biol. 27, 5523-5533.
27. Bourn R. L., Rindler P. M., Pollard L. M., and, Bidichandani S. I., (2009) E. coli mismatch repair acts downstream of replication fork stalling to stabilize the expanded (GAA.TTC)(n) sequence. Mutat. Res. 661, 71-77.
28. Brookes E., de Santiago I., Hebenstreit D., et al,. (2012) Polycomb associates genome-wide with a specific RNA polymerase II variant, and regulates metabolic genes in ESCs. Cell Stem Cell 10, 157-170.
29. Burnett R., Melander C., Puckett J. W., Son L. S., Wells R. D., Dervan P. B., and, Gottesfeld J. M., (2006) DNA sequence-specific polyamides alleviate transcription inhibition associated with long GAA.TTC repeats in Friedreich's ataxia. Proc. Natl Acad. Sci. USA 103, 11497-11502.
30. Bushey A. M., Dorman E. R., and, Corces V. G., (2008) Chromatin insulators: regulatory mechanisms and epigenetic inheritance. Mol. Cell 32, 1-9.
31. Buxton J., Shelbourne P., Davies J., et al,. (1992) Detection of an unstable fragment of DNA specific to individuals with myotonic dystrophy. Nature 355, 547-548.
32. Cabianca D. S., Casa V., Bodega B., Xynos A., Ginelli E., Tanaka Y., and, Gabellini D., (2012) A long ncRNA links copy number variation to a polycomb/trithorax epigenetic switch in FSHD muscular dystrophy. Cell 149, 819-831.
33. Campuzano V., Montermini L., Molto M. D., et al,. (1996) Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 271, 1423-1427.
34. Campuzano V., Montermini L., Lutz Y., et al,. (1997) Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes. Hum. Mol. Genet. 6, 1771-1780.
35. Cao R., Tsukada Y., and, Zhang Y., (2005) Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing. Mol. Cell 20, 845-854.
36. Caplen N. J., Parrish S., Imani F., Fire A., and, Morgan R. A., (2001) Specific inhibition of gene expression by small double-stranded RNAs in invertebrate and vertebrate systems. Proc. Natl Acad. Sci. USA 98, 9742-9747.
37. Castaldo I., Pinelli M., Monticelli A., et al,. (2008) DNA methylation in intron 1 of the frataxin gene is related to GAA repeat length and age of onset in Friedreich ataxia patients. J. Med. Genet. 45, 808-812.
38. Chernukhin I., Shamsuddin S., Kang S. Y., et al,. (2007) CTCF interacts with and recruits the largest subunit of RNA polymerase II to CTCF target sites genome-wide. Mol. Cell. Biol. 27, 1631-1648.
39. Chan P. K., Torres R., Yandim C,. et al. (2013) Heterochromatinization induced by GAA-repeat hyperexpansion in Friedreich's ataxia can be reduced upon HDAC inhibition by vitamin B3. Hum. Mol. Genet [Epub ahead of print].
40. Cho D. H., and, Tapscott S. J., (2007) Myotonic dystrophy: emerging mechanisms for DM1 and DM2. Biochim. Biophys. Acta 1772, 195-204.
41. Cho D. H., Thienes C. P., Mahoney S. E., Analau E., Filippova G. N., and, Tapscott S. J., (2005) Antisense transcription and heterochromatin at the DM1 CTG repeats are constrained by CTCF. Mol. Cell 20, 483-489.
42. Chou S. H., Chin K. H., and, Wang A. H., (2003) Unusual DNA duplex and hairpin motifs. Nucleic Acids Res. 31, 2461-2474.
43. Chung J. H., Whiteley M., and, Felsenfeld G., (1993) A 5′ element of the chicken beta-globin domain serves as an insulator in human erythroid cells and protects against position effect in Drosophila. Cell 74, 505-514.
44. Chung J. H., Bell A. C., and, Felsenfeld G., (1997) Characterization of the chicken beta-globin insulator. Proc. Natl Acad. Sci. USA 94, 575-580.
45. Clark R. M., Dalgliesh G. L., Endres D., Gomez M., Taylor J., and, Bidichandani S. I., (2004) Expansion of GAA triplet repeats in the human genome: unique origin of the FRDA mutation at the center of an Alu. Genomics 83, 373-383.
46. Clark R. M., De Biase I., Malykhina A. P., Al-Mahdawi S., Pook M., and, Bidichandani S. I., (2007) The GAA triplet-repeat is unstable in the context of the human FXN locus and displays age-dependent expansions in cerebellum and DRG in a transgenic mouse model. Hum. Genet. 120, 633-640.
47. Coppola G., Marmolino D., Lu D., Wang Q., Cnop M., Rai M., Acquaviva F., Cocozza S., Pandolfo M., and, Geschwind D. H., (2009) Functional genomic analysis of frataxin deficiency reveals tissue-specific alterations and identifies the PPARgamma pathway as a therapeutic target in Friedreich's ataxia. Hum. Mol. Genet. 18, 2452-2461.
48. Cossee M., Schmitt M., Campuzano V., Reutenauer L., Moutou C., Mandel J. L., and, Koenig M., (1997) Evolution of the Friedreich's ataxia trinucleotide repeat expansion: founder effect and premutations. Proc. Natl Acad. Sci. USA 94, 7452-7457.
49. De Biase I., Rasmussen A., Endres D., Al-Mahdawi S., Monticelli A., Cocozza S., Pook M., and, Bidichandani S. I., (2007) Progressive GAA expansions in dorsal root ganglia of Friedreich's ataxia patients. Ann. Neurol. 61, 55-60.
50. De Biase I., Chutake Y. K., Rindler P. M., and, Bidichandani S. I., (2009) Epigenetic silencing in Friedreich ataxia is associated with depletion of CTCF (CCCTC-binding factor) and antisense transcription. PLoS ONE 4, e7914.
51. Dhasarathy A., and, Wade P. A., (2008) The MBD protein family-reading an epigenetic mark? Mutat. Res. 647, 39-43.
52. D'Hulst C., and, Kooy R. F., (2009) Fragile X syndrome: from molecular genetics to therapy. J. Med. Genet. 46, 577-584.
53. Dillon N., (2004) Heterochromatin structure and function. Biol. Cell 96, 631-637.
54. Dillon N., and, Festenstein R., (2002) Unravelling heterochromatin: competition between positive and negative factors regulates accessibility. Trends Genet. 18, 252-258.
55. Dion M. F., Altschuler S. J., Wu L. F., and, Rando O. J., (2005) Genomic characterization reveals a simple histone H4 acetylation code. Proc. Natl Acad. Sci. USA 102, 5501-5506.
56. Djebali S., Davis C. A., Merkel A., et al,. (2012) Landscape of transcription in human cells. Nature 489, 101-108.
57. Djupedal I., and, Ekwall K., (2009) Epigenetics: heterochromatin meets RNAi. Cell Res. 19, 282-295.
58. Du J., Campau E., Soragni E., Ku S., Puckett J. W., Dervan P. B., and, Gottesfeld J. M., (2012) Role of Mismatch Repair Enzymes in GAA{middle dot}TTC Triplet-repeat Expansion in Friedreich Ataxia Induced Pluripotent Stem Cells. J. Biol. Chem. 287, 29861-29872.
59. Dunham I., Kundaje A., Aldred S. F., et al,. (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57-74.
60. Durr A., Cossee M., Agid Y., Campuzano V., Mignard C., Penet C., Mandel J. L., Brice A., and, Koenig M., (1996) Clinical and genetic abnormalities in patients with Friedreich's ataxia. N. Engl. J. Med. 335, 1169-1175.
61. Eckert D., Buhl S., Weber S., Jager R., and, Schorle H., (2005) The AP-2 family of transcription factors. Genome Biol. 6, 246.
62. Eiges R., Urbach A., Malcov M., et al,. (2007) Developmental study of fragile X syndrome using human embryonic stem cells derived from preimplantation genetically diagnosed embryos. Cell Stem Cell 1, 568-577.
63. Elbashir S. M., Harborth J., Lendeckel W., Yalcin A., Weber K., and, Tuschl T., (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411, 494-498.
64. Elgin S. C., (1996) Heterochromatin and gene regulation in Drosophila. Curr. Opin. Genet. Dev. 6, 193-202.
65. Englander E. W., and, Howard B. H., (1995) Nucleosome positioning by human Alu elements in chromatin. J. Biol. Chem. 270, 10091-10096.
66. Evans-Galea M. V., Carrodus N., Rowley S. M., et al,. (2012) FXN methylation predicts expression and clinical outcome in Friedreich ataxia. Ann. Neurol. 71, 487-497.
67. Ezzatizadeh V., Pinto R. M., Sandi C., Sandi M., Al-Mahdawi S., Te Riele H., and, Pook M. A., (2012) The mismatch repair system protects against intergenerational GAA repeat instability in a Friedreich ataxia mouse model. Neurobiol. Dis. 46, 165-171.
68. Faghihi M. A., and, Wahlestedt C., (2009) Regulatory roles of natural antisense transcripts. Nat. Rev. Mol. Cell Biol. 10, 637-643.
69. Festenstein R., (2006) Breaking the silence in Friedreich's ataxia. Nat. Chem. Biol. 2, 512-513.
70. Festenstein R., Tolaini M., Corbella P., Mamalaki C., Parrington J., Fox M., Miliou A., Jones M., and, Kioussis D., (1996) Locus control region function and heterochromatin-induced position effect variegation. Science 271, 1123-1125.
71. Festenstein R., Sharghi-Namini S., Fox M., Roderick K., Tolaini M., Norton T., Saveliev A., Kioussis D., and, Singh P., (1999) Heterochromatin protein 1 modifies mammalian PEV in a dose- and chromosomal-context-dependent manner. Nat. Genet. 23, 457-461.
72. Filippova G. N., Thienes C. P., Penn B. H., Cho D. H., Hu Y. J., Moore J. M., Klesert T. R., Lobanenkov V. V., and, Tapscott S. J., (2001) CTCF-binding sites flank CTG/CAG repeats and form a methylation-sensitive insulator at the DM1 locus. Nat. Genet. 28, 335-343.
73. Filla A., De Michele G., Cavalcanti F., Pianese L., Monticelli A., Campanella G., and, Cocozza S,. (1996). The relationship between trinucleotide (GAA) repeat length and clinical features in Friedreich ataxia. Am. J. Hum. Genet. 59, 554-560.
74. Fire A., Xu S., Montgomery M. K., Kostas S. A., Driver S. E., and, Mello C. C., (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391, 806-811.
75. Fischle W., Wang Y., Jacobs S. A., Kim Y., Allis C. D., and, Khorasanizadeh S., (2003) Molecular basis for the discrimination of repressive methyl-lysine marks in histone H3 by Polycomb and HP1 chromodomains. Genes Dev. 17, 1870-1881.
76. Fisher A. G., and, Merkenschlager M., (2002) Gene silencing, cell fate and nuclear organisation. Curr. Opin. Genet. Dev. 12, 193-197.
77. Fleming J., Spinoulas A., Zheng M., Cunningham S. C., Ginn S. L., McQuilty R. C., Rowe P. B., and, Alexander I. E., (2005) Partial correction of sensitivity to oxidant stress in Friedreich ataxia patient fibroblasts by frataxin-encoding adeno-associated virus and lentivirus vectors. Hum. Gene Ther. 16, 947-956.
78. Francis N. J., Kingston R. E., and, Woodcock C. L., (2004) Chromatin compaction by a polycomb group protein complex. Science 306, 1574-1577.
79. Fukagawa T., Nogami M., Yoshikawa M., Ikeno M., Okazaki T., Takami Y., Nakayama T., and, Oshimura M., (2004) Dicer is essential for formation of the heterochromatin structure in vertebrate cells. Nat. Cell Biol. 6, 784-791.
80. Fuks F., Hurd P. J., Deplus R., and, Kouzarides T., (2003) The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase. Nucleic Acids Res. 31, 2305-2312.
81. Gacy A. M., Goellner G. M., Spiro C., et al,. (1998) GAA instability in Friedreich's Ataxia shares a common, DNA-directed and intraallelic mechanism with other trinucleotide diseases. Mol. Cell 1, 583-593.
82. Geiman T. M., and, Muegge K., (2010) DNA methylation in early development. Mol. Reprod. Dev. 77, 105-113.
83. Goodarzi A. A., Noon A. T., Deckbar D., Ziv Y., Shiloh Y., Lobrich M., and, Jeggo P. A., (2008) ATM signaling facilitates repair of DNA double-strand breaks associated with heterochromatin. Mol. Cell 31, 167-177.
84. Gottesfeld J. M., (2007) Small molecules affecting transcription in Friedreich ataxia. Pharmacol. Ther. 116, 236-248.
85. Gottesfeld J., Rusche J. R., Pandolfo M., (2013) Increasing frataxin fene expression with histone deacetylase inhibitors as a therapeutic approach for Friedreich's ataxia. J. Neurochem 126 (Suppl. 1), 147-154.
86. Grabczyk E., and, Usdin K., (2000a) Alleviating transcript insufficiency caused by Friedreich's ataxia triplet repeats. Nucleic Acids Res. 28, 4930-4937.
87. Grabczyk E., and, Usdin K., (2000b) The GAA*TTC triplet repeat expanded in Friedreich's ataxia impedes transcription elongation by T7 RNA polymerase in a length and supercoil dependent manner. Nucleic Acids Res. 28, 2815-2822.
88. Grabczyk E., Mancuso M., and, Sammarco M. C., (2007) A persistent RNA.DNA hybrid formed by transcription of the Friedreich ataxia triplet repeat in live bacteria, and by T7 RNAP in vitro. Nucleic Acids Res. 35, 5351-5359.
89. Grau D. J., Chapman B. A., Garlick J. D., Borowsky M., Francis N. J., and, Kingston R. E., (2011) Compaction of chromatin by diverse Polycomb group proteins requires localized regions of high charge. Genes Dev. 25, 2210-2221.
90. Greene E., Entezam A., Kumari D., and, Usdin K., (2005) Ancient repeated DNA elements and the regulation of the human frataxin promoter. Genomics 85, 221-230.
91. Greene E., Mahishi L., Entezam A., Kumari D., and, Usdin K., (2007) Repeat-induced epigenetic changes in intron 1 of the frataxin gene and its consequences in Friedreich ataxia. Nucleic Acids Res. 35, 3383-3390.
92. Guenatri M., Bailly D., Maison C., and, Almouzni G., (2004) Mouse centric and pericentric satellite repeats form distinct functional heterochromatin. J. Cell Biol. 166, 493-505.
93. Halleck M. S., and, Gurley L. R., (1981) Histone acetylation and heterochromatin content of cultured Peromyscus cells. Exp. Cell Res. 132, 201-213.
94. Hanawalt P. C., and, Spivak G., (2008) Transcription-coupled DNA repair: two decades of progress and surprises. Nat. Rev. Mol. Cell Biol. 9, 958-970.
95. Harrow J., Frankish A., Gonzalez J. M., et al,. (2012) GENCODE: the reference human genome annotation for The ENCODE Project. Genome Res. 22, 1760-1774.
96. Hassan A. H., Prochasson P., Neely K. E., Galasinski S. C., Chandy M., Carrozza M. J., and, Workman J. L., (2002) Function and selectivity of bromodomains in anchoring chromatin-modifying complexes to promoter nucleosomes. Cell 111, 369-379.
97. Hebbes T. R., Thorne A. W., and, Crane-Robinson C., (1988) A direct link between core histone acetylation and transcriptionally active chromatin. EMBO J. 7, 1395-1402.
98. Heidenfelder B. L., Makhov A. M., and, Topal M. D., (2003) Hairpin formation in Friedreich's ataxia triplet repeat expansion. J. Biol. Chem. 278, 2425-2431.
99. Heitz E., (1928) Das Heterochromatin der Moose. Jahrb. Wiss. Bot. 69, 762.
100. Herman D., Jenssen K., Burnett R., Soragni E., Perlman S. L., and, Gottesfeld J. M., (2006) Histone deacetylase inhibitors reverse gene silencing in Friedreich's ataxia. Nat. Chem. Biol. 2, 551-558.
101. Holliday R., and, Pugh J. E., (1975) DNA modification mechanisms and gene activity during development. Science 187, 226-232.
102. Hong L., Schroth G. P., Matthews H. R., Yau P., and, Bradbury E. M., (1993) Studies of the DNA binding properties of histone H4 amino terminus. Thermal denaturation studies reveal that acetylation markedly reduces the binding constant of the H4 "tail" to DNA. J. Biol. Chem. 268, 305-314.
103. Hublitz P., Albert M., and, Peters A. H., (2009) Mechanisms of transcriptional repression by histone lysine methylation. Int. J. Dev. Biol. 53, 335-354.
104. Ip J., Canham P., Choo K. H., et al,. (2012) Normal DNA Methylation Dynamics in DICER1-Deficient Mouse Embryonic Stem Cells. PLoS Genet. 8, e1002919.
105. Jain A., Rajeswari M. R., and, Ahmed F., (2002) Formation and thermodynamic stability of intermolecular (R*R*Y) DNA triplex in GAA/TTC repeats associated with Freidreich's ataxia. J. Biomol. Struct. Dyn. 19, 691-699.
106. Jenuwein T., and, Allis C. D., (2001) Translating the histone code. Science 293, 1074-1080.
107. Justice C. M., Den Z., Nguyen S. V., Stoneking M., Deininger P. L., Batzer M. A., and, Keats B. J., (2001) Phylogenetic analysis of the Friedreich ataxia GAA trinucleotide repeat. J. Mol. Evol. 52, 232-238.
108. Kelly D. P., and, Scarpulla R. C., (2004) Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev. 18, 357-368.
109. Kim C. A., Gingery M., Pilpa R. M., and, Bowie J. U., (2002) The SAM domain of polyhomeotic forms a helical polymer. Nat. Struct. Biol. 9, 453-457.
110. Kim H. M., Narayanan V., Mieczkowski P. A., Petes T. D., Krasilnikova M. M., Mirkin S. M., and, Lobachev K. S., (2008) Chromosome fragility at GAA tracts in yeast depends on repeat orientation and requires mismatch repair. EMBO J. 27, 2896-2906.
111. Kim E., Napierala M., and, Dent S. Y., (2011) Hyperexpansion of GAA repeats affects post-initiation steps of FXN transcription in Friedreich's ataxia. Nucleic Acids Res. 39, 8366-8377.
112. Knoll B., and, Nordheim A., (2009) Functional versatility of transcription factors in the nervous system: the SRF paradigm. Trends Neurosci. 32, 432-442.
113. Koutnikova H., Campuzano V., Foury F., Dolle P., Cazzalini O., and, Koenig M., (1997) Studies of human, mouse and yeast homologues indicate a mitochondrial function for frataxin. Nat. Genet. 16, 345-351.
114. Kouzarides T., (2007) Chromatin modifications and their function. Cell 128, 693-705.
115. Krasilnikova M. M., Kireeva M. L., Petrovic V., Knijnikova N., Kashlev M., and, Mirkin S. M., (2007) Effects of Friedreich's ataxia (GAA)n*(TTC)n repeats on RNA synthesis and stability. Nucleic Acids Res. 35, 1075-1084.
116. Ku S., Soragni E., Campau E., Thomas E. A., Altun G., Laurent L. C., Loring J. F., Napierala M., and, Gottesfeld J. M., (2010) Friedreich's ataxia induced pluripotent stem cells model intergenerational GAATTC triplet repeat instability. Cell Stem Cell 7, 631-637.
117. Kumari D., and, Usdin K., (2010) The distribution of repressive histone modifications on silenced FMR1 alleles provides clues to the mechanism of gene silencing in fragile X syndrome. Hum. Mol. Genet. 19, 4634-4642.
118. Kumari D., and, Usdin K., (2012) Is Friedreich ataxia an epigenetic disorder? Clin. Epigenetics 4, 2.
119. Kumari D., Biacsi R. E., and, Usdin K., (2011) Repeat expansion affects both transcription initiation and elongation in friedreich ataxia cells. J. Biol. Chem. 286, 4209-4215.
120. Lachner M., O'Carroll D., Rea S., Mechtler K., and, Jenuwein T., (2001) Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410, 116-120.
121. Ladd P. D., Smith L. E., Rabaia N. A., Moore J. M., Georges S. A., Hansen R. S., Hagerman R. J., Tassone F., Tapscott S. J., and, Filippova G. N., (2007) An antisense transcript spanning the CGG repeat region of FMR1 is upregulated in premutation carriers but silenced in full mutation individuals. Hum. Mol. Genet. 16, 3174-3187.
122. Lander E. S., Linton L. M., Birren B., et al,. (2001) Initial sequencing and analysis of the human genome. Nature 409, 860-921.
123. Lee D. Y., Teyssier C., Strahl B. D., and, Stallcup M. R., (2005) Role of protein methylation in regulation of transcription. Endocr. Rev. 26, 147-170.
124. Lehnertz B., Ueda Y., Derijck A. A., Braunschweig U., Perez-Burgos L., Kubicek S., Chen T., Li E., Jenuwein T., and, Peters A. H., (2003) Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin. Curr. Biol. 13, 1192-1200.
125. LeProust E. M., Pearson C. E., Sinden R. R., and, Gao X., (2000) Unexpected formation of parallel duplex in GAA and TTC trinucleotide repeats of Friedreich's ataxia. J. Mol. Biol. 302, 1063-1080.
126. Li E., Bestor T. H., and, Jaenisch R., (1992) Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69, 915-926.
127. Li K., Besse E. K., Ha D., Kovtunovych G., and, Rouault T. A., (2008) Iron-dependent regulation of frataxin expression: implications for treatment of Friedreich ataxia. Hum. Mol. Genet. 17, 2265-2273.
128. Li K., Singh A., Crooks D. R., Dai X., Cong Z., Pan L., Ha D., and, Rouault T. A., (2010) Expression of human frataxin is regulated by transcription factors SRF and TFAP2. PLoS ONE 5, e12286.
129. Liu W. M., and, Schmid C. W., (1993) Proposed roles for DNA methylation in Alu transcriptional repression and mutational inactivation. Nucleic Acids Res. 21, 1351-1359.
130. Locke J., Kotarski M. A., and, Tartof K. D., (1988) Dosage-dependent modifiers of position effect variegation in Drosophila and a mass action model that explains their effect. Genetics 120, 181-198.
131. Lopez Castel A., Nakamori M., Tome S., Chitayat D., Gourdon G., Thornton C. A., and, Pearson C. E., (2011) Expanded CTG repeat demarcates a boundary for abnormal CpG methylation in myotonic dystrophy patient tissues. Hum. Mol. Genet. 20, 1-15.
132. Luger K., Mader A. W., Richmond R. K., Sargent D. F., and, Richmond T. J., (1997) Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature 389, 251-260.
133. Luijsterburg M. S., Dinant C., Lans H., et al,. (2009) Heterochromatin protein 1 is recruited to various types of DNA damage. J. Cell Biol. 185, 577-586.
134. van der Maarel S. M., Tawil R., and, Tapscott S. J., (2011) Facioscapulohumeral muscular dystrophy and DUX4: breaking the silence. Trends Mol. Med. 17, 252-258.
135. Mahadevan M., Tsilfidis C., Sabourin L., et al,. (1992) Myotonic dystrophy mutation: an unstable CTG repeat in the 3′ untranslated region of the gene. Science 255, 1253-1255.
136. Maison C., Bailly D., Peters A. H., Quivy J. P., Roche D., Taddei A., Lachner M., Jenuwein T., and, Almouzni G., (2002) Higher-order structure in pericentric heterochromatin involves a distinct pattern of histone modification and an RNA component. Nat. Genet. 30, 329-334.
137. Maison C., Bailly D., Roche D., et al,. (2011) SUMOylation promotes de novo targeting of HP1alpha to pericentric heterochromatin. Nat. Genet. 43, 220-227.
138. Margueron R., and, Reinberg D., (2010) Chromatin structure and the inheritance of epigenetic information. Nat. Rev. Genet. 11, 285-296.
139. Mariappan S. V., Catasti P., Silks L. A., 3rd, Bradbury E. M., and, Gupta G., (1999) The high-resolution structure of the triplex formed by the GAA/TTC triplet repeat associated with Friedreich's ataxia. J. Mol. Biol. 285, 2035-2052.
140. Marmolino D., Acquaviva F., Pinelli M., Monticelli A., Castaldo I., Filla A., and, Cocozza S., (2009) PPAR-gamma agonist Azelaoyl PAF increases frataxin protein and mRNA expression: new implications for the Friedreich's ataxia therapy. Cerebellum 8, 98-103.
141. Marmolino D., Manto M., Acquaviva F., Vergara P., Ravella A., Monticelli A., and, Pandolfo M., (2010) PGC-1alpha down-regulation affects the antioxidant response in Friedreich's ataxia. PLoS ONE 5, e10025.
142. Martin C., and, Zhang Y., (2005) The diverse functions of histone lysine methylation. Nat. Rev. Mol. Cell Biol. 6, 838-849.
143. Maston G. A., Evans S. K., and, Green M. R., (2006) Transcriptional regulatory elements in the human genome. Annu. Rev. Genomics Hum. Genet. 7, 29-59.
144. McIvor E. I., Polak U., and, Napierala M., (2010) New insights into repeat instability: role of RNA*DNA hybrids. RNA Biol. 7, 551-558.
145. Mellon I., Spivak G., and, Hanawalt P. C., (1987) Selective removal of transcription-blocking DNA damage from the transcribed strand of the mammalian DHFR gene. Cell 51, 241-249.
146. Mikkelsen T. S., Ku M., Jaffe D. B., et al,. (2007) Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448, 553-560.
147. Mirkin S. M., (2007) Expandable DNA repeats and human disease. Nature 447, 932-940.
148. Monros E., Molto M. D., Martinez F., Canizares J., Blanca J., Vilchez J. J., Prieto F., de Frutos R., and, Palau F., (1997) Phenotype correlation and intergenerational dynamics of the Friedreich ataxia GAA trinucleotide repeat. Am. J. Hum. Genet. 61, 101-110.
149. Montermini L., Andermann E., Labuda M., et al,. (1997a) The Friedreich ataxia GAA triplet repeat: premutation and normal alleles. Hum. Mol. Genet. 6, 1261-1266.
150. Montermini L., Richter A., Morgan K., et al,. (1997b) Phenotypic variability in Friedreich ataxia: role of the associated GAA triplet repeat expansion. Ann. Neurol. 41, 675-682.
151. Monticelli A., Giacchetti M., De Biase I., Pianese L., Turano M., Pandolfo M., and, Cocozza S., (2004) New clues on the origin of the Friedreich ataxia expanded alleles from the analysis of new polymorphisms closely linked to the mutation. Hum. Genet. 114, 458-463.
152. Morris K. V., Santoso S., Turner A. M., Pastori C., and, Hawkins P. G., (2008) Bidirectional transcription directs both transcriptional gene activation and suppression in human cells. PLoS Genet. 4, e1000258.
153. Mottus R., Sobel R. E., and, Grigliatti T. A., (2000) Mutational analysis of a histone deacetylase in Drosophila melanogaster: missense mutations suppress gene silencing associated with position effect variegation. Genetics 154, 657-668.
154. Muller H., (1930) Types of visible variations induced by X-rays in Drosophila. J. Genet. 22, 299-334.
155. Murchison E. P., Partridge J. F., Tam O. H., Cheloufi S., and, Hannon G. J., (2005) Characterization of Dicer-deficient murine embryonic stem cells. Proc. Natl Acad. Sci. USA 102, 12135-12140.
156. Murre C., McCaw P. S., Vaessin H., et al,. (1989) Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell 58, 537-544.
157. Naumann A., Hochstein N., Weber S., Fanning E., and, Doerfler W., (2009) A distinct DNA-methylation boundary in the 5′- upstream sequence of the FMR1 promoter binds nuclear proteins and is lost in fragile X syndrome. Am. J. Hum. Genet. 85, 606-616.
158. Navarro J. A., Llorens J. V., Soriano S., Botella J. A., Schneuwly S., Martinez-Sebastian M. J., and, Molto M. D., (2011) Overexpression of human and fly frataxins in Drosophila provokes deleterious effects at biochemical, physiological and developmental levels. PLoS ONE 6, e21017.
159. Ng H. H., Robert F., Young R. A., and, Struhl K., (2003) Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity. Mol. Cell 11, 709-719.
160. Nguyen A. T., and, Zhang Y., (2011) The diverse functions of Dot1 and H3K79 methylation. Genes Dev. 25, 1345-1358.
161. Nigumann P., Redik K., Matlik K., and, Speek M., (2002) Many human genes are transcribed from the antisense promoter of L1 retrotransposon. Genomics 79, 628-634.
162. Norris J., Fan D., Aleman C., Marks J. R., Futreal P. A., Wiseman R. W., Iglehart J. D., Deininger P. L., and, McDonnell D. P., (1995) Identification of a new subclass of Alu DNA repeats which can function as estrogen receptor-dependent transcriptional enhancers. J. Biol. Chem. 270, 22777-22782.
163. Ohno M., Fukagawa T., Lee J. S., and, Ikemura T., (2002) Triplex-forming DNAs in the human interphase nucleus visualized in situ by polypurine/ polypyrimidine DNA probes and antitriplex antibodies. Chromosoma 111, 201-213.
164. Ohshima K., Montermini L., Wells R. D., and, Pandolfo M., (1998) Inhibitory effects of expanded GAA.TTC triplet repeats from intron I of the Friedreich ataxia gene on transcription and replication in vivo. J. Biol. Chem. 273, 14588-14595.
165. Okano M., Bell D. W., Haber D. A., and, Li E., (1999) DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99, 247-257.
166. Oliviero S., and, Monaci P., (1988) RNA polymerase III promoter elements enhance transcription of RNA polymerase II genes. Nucleic Acids Res. 16, 1285-1293.
167. Pastore A., and, Puccio H,. (2013) Frataxin: a protein in search for a function. J. Neurochem 126 (Suppl. 1), 43-52.
168. Peng J. C., and, Karpen G. H., (2009) Heterochromatic genome stability requires regulators of histone H3 K9 methylation. PLoS Genet. 5, e1000435.
169. Peters A. H., O'Carroll D., Scherthan H., et al,. (2001) Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability. Cell 107, 323-337.
170. Peters A. H., Kubicek S., Mechtler K., et al,. (2003) Partitioning and plasticity of repressive histone methylation states in mammalian chromatin. Mol. Cell 12, 1577-1589.
171. Peters J. M., Tedeschi A., and, Schmitz J., (2008) The cohesin complex and its roles in chromosome biology. Genes Dev. 22, 3089-3114.
172. Piedrafita F. J., Molander R. B., Vansant G., Orlova E. A., Pfahl M., and, Reynolds W. F., (1996) An Alu element in the myeloperoxidase promoter contains a composite SP1-thyroid hormone-retinoic acid response element. J. Biol. Chem. 271, 14412-14420.
173. Pieretti M., Zhang F. P., Fu Y. H., Warren S. T., Oostra B. A., Caskey C. T., and, Nelson D. L., (1991) Absence of expression of the FMR-1 gene in fragile X syndrome. Cell 66, 817-822.
174. Pietrobono R., Tabolacci E., Zalfa F., Zito I., Terracciano A., Moscato U., Bagni C., Oostra B., Chiurazzi P., and, Neri G., (2005) Molecular dissection of the events leading to inactivation of the FMR1 gene. Hum. Mol. Genet. 14, 267-277.
175. Potaman V. N., Oussatcheva E. A., Lyubchenko Y. L., Shlyakhtenko L. S., Bidichandani S. I., Ashizawa T., and, Sinden R. R., (2004) Length-dependent structure formation in Friedreich ataxia (GAA)n*(TTC)n repeats at neutral pH. Nucleic Acids Res. 32, 1224-1231.
176. Pradhan S., Bacolla A., Wells R. D., and, Roberts R. J., (1999) Recombinant human DNA (cytosine-5) methyltransferase. I. Expression,
177. Probst A. V., Dunleavy E., and, Almouzni G., (2009) Epigenetic inheritance during the cell cycle. Nat. Rev. Mol. Cell Biol. 10, 192-206.
178. Punga T., and, Buhler M., (2010) Long intronic GAA repeats causing Friedreich ataxia impede transcription elongation. EMBO Mol. Med. 2, 120-129.
179. Rai M., Soragni E., Chou C. J., Barnes G., Jones S., Rusche J. R., Gottesfeld J. M., and, Pandolfo M., (2010) Two new pimelic diphenylamide HDAC inhibitors induce sustained frataxin upregulation in cells from Friedreich's ataxia patients and in a mouse model. PLoS ONE 5, e8825.
180. Ramchandani S., Bhattacharya S. K., Cervoni N., and, Szyf M., (1999) DNA methylation is a reversible biological signal. Proc. Natl Acad. Sci. USA 96, 6107-6112.
181. Rando O. J., and, Chang H. Y., (2009) Genome-wide views of chromatin structure. Annu. Rev. Biochem. 78, 245-271.
182. Rea S., Eisenhaber F., O'Carroll D., et al,. (2000) Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature 406, 593-599.
183. Reinhart B. J., and, Bartel D. P., (2002) Small RNAs correspond to centromere heterochromatic repeats. Science 297, 1831.
184. Reuter G., and, Spierer P., (1992) Position effect variegation and chromatin proteins. BioEssays 14, 605-612.
185. Reuter G., Gausz J., Gyurkovics H., Friede B., Bang R., Spierer A., Hall L. M., and, Spierer P., (1987) Modifiers of position-effect variegation in the region from 86C to 88B of the Drosophila melanogaster third chromosome. Mol. Gen. Genet. 210, 429-436.
186. Richard G. F., Kerrest A., and, Dujon B., (2008) Comparative genomics and molecular dynamics of DNA repeats in eukaryotes. Microbiol. Mol. Biol. Rev. 72, 686-727.
187. Riggs A. D., (1975) X inactivation, differentiation, and DNA methylation. Cytogenet. Cell Genet. 14, 9-25.
188. Robertson K. D., (2005) DNA methylation and human disease. Nat. Rev. Genet. 6, 597-610.
189. Ronai D., Iglesias-Ussel M. D., Fan M., Li Z., Martin A., and, Scharff M. D., (2007) Detection of chromatin-associated single-stranded DNA in regions targeted for somatic hypermutation. J. Exp. Med. 204, 181-190.
190. Rothe N,. (2008). Ph.D. Thesis: Gene regulation and epigenotype in Friedreich's ataxia. Imperial College London, London.
191. Rotig A., de Lonlay P., Chretien D., Foury F., Koenig M., Sidi D., Munnich A., and, Rustin P., (1997) Aconitase and mitochondrial iron-sulphur protein deficiency in Friedreich ataxia. Nat. Genet. 17, 215-217.
192. Rouault T. A., and, Tong W. H., (2005) Iron-sulphur cluster biogenesis and mitochondrial iron homeostasis. Nat. Rev. Mol. Cell Biol. 6, 345-351.
193. Sacca F., Puorro G., Antenora A., et al,. (2011) A combined nucleic acid and protein analysis in Friedreich ataxia: implications for diagnosis, pathogenesis and clinical trial design. PLoS ONE 6, e17627.
194. Sakamoto N., Chastain P. D., Parniewski P., Ohshima K., Pandolfo M., Griffith J. D., and, Wells R. D., (1999) Sticky DNA: self-association properties of long GAA.TTC repeats in R.R.Y triplex structures from Friedreich's ataxia. Mol. Cell 3, 465-475.
195. Sakamoto N., Ohshima K., Montermini L., Pandolfo M., and, Wells R. D., (2001) Sticky DNA, a self-associated complex formed at long GAA*TTC repeats in intron 1 of the frataxin gene, inhibits transcription. J. Biol. Chem. 276, 27171-27177.
196. Sandi C., Pinto R. M., Al-Mahdawi S., Ezzatizadeh V., Barnes G., Jones S., Rusche J. R., Gottesfeld J. M., and, Pook M. A., (2011) Prolonged treatment with pimelic o-aminobenzamide HDAC inhibitors ameliorates the disease phenotype of a Friedreich ataxia mouse model. Neurobiol. Dis. 42, 496-505.
197. Santos-Rosa H., Schneider R., Bannister A. J., Sherriff J., Bernstein B. E., Emre N. C., Schreiber S. L., Mellor J., and, Kouzarides T., (2002) Active genes are tri-methylated at K4 of histone H3. Nature 419, 407-411.
198. Saunders A., Core L. J., and, Lis J. T., (2006) Breaking barriers to transcription elongation. Nat. Rev. Mol. Cell Biol. 7, 557-567.
199. Saveliev A., Everett C., Sharpe T., Webster Z., and, Festenstein R., (2003) DNA triplet repeats mediate heterochromatin-protein-1-sensitive variegated gene silencing. Nature 422, 909-913.
200. Schotta G., Ebert A., Krauss V., Fischer A., Hoffmann J., Rea S., Jenuwein T., Dorn R., and, Reuter G., (2002) Central role of Drosophila SU(VAR)3-9 in histone H3-K9 methylation and heterochromatic gene silencing. EMBO J. 21, 1121-1131.
201. Schulz W. A., Steinhoff C., and, Florl A. R., (2006) Methylation of endogenous human retroelements in health and disease. Curr. Top. Microbiol. Immunol. 310, 211-250.
202. Schwartz J. C., Younger S. T., Nguyen N. B., Hardy D. B., Monia B. P., Corey D. R., and, Janowski B. A., (2008) Antisense transcripts are targets for activating small RNAs. Nat. Struct. Mol. Biol. 15, 842-848.
203. Sealy L., and, Chalkley R., (1978) DNA associated with hyperacetylated histone is preferentially digested by DNase I. Nucleic Acids Res. 5, 1863-1876.
204. Shahbazian M. D., and, Grunstein M., (2007) Functions of site-specific histone acetylation and deacetylation. Annu. Rev. Biochem. 76, 75-100.
205. Shen L., Kondo Y., Guo Y., Zhang J., Zhang L., Ahmed S., Shu J., Chen X., Waterland R. A., and, Issa J. P., (2007) Genome-wide profiling of DNA methylation reveals a class of normally methylated CpG island promoters. PLoS Genet. 3, 2023-2036.
206. Shishkin A. A., Voineagu I., Matera R., Cherng N., Chernet B. T., Krasilnikova M. M., Narayanan V., Lobachev K. S., and, Mirkin S. M., (2009) Large-scale expansions of Friedreich's ataxia GAA repeats in yeast. Mol. Cell 35, 82-92.
207. Shogren-Knaak M., Ishii H., Sun J. M., Pazin M. J., Davie J. R., and, Peterson C. L., (2006) Histone H4-K16 acetylation controls chromatin structure and protein interactions. Science 311, 844-847.
208. Snider L., Geng L. N., Lemmers R. J., et al,. (2010) Facioscapulohumeral dystrophy: incomplete suppression of a retrotransposed gene. PLoS Genet. 6, e1001181.
209. Soragni E., Herman D., Dent S. Y., Gottesfeld J. M., Wells R. D., and, Napierala M., (2008) Long intronic GAA*TTC repeats induce epigenetic changes and reporter gene silencing in a molecular model of Friedreich ataxia. Nucleic Acids Res. 36, 6056-6065.
210. Splinter E., Heath H., Kooren J., Palstra R. J., Klous P., Grosveld F., Galjart N., and, de Laat W., (2006) CTCF mediates long-range chromatin looping and local histone modification in the beta-globin locus. Genes Dev. 20, 2349-2354.
211. Sterner D. E., and, Berger S. L., (2000) Acetylation of histones and transcription-related factors. Microbiol. Mol. Biol. Rev. 64, 435-459.
212. Strausberg R. L., Feingold E. A., Grouse L. H., et al,. (2002) Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proc. Natl Acad. Sci. USA 99, 16899-16903.
213. Su A. I., Wiltshire T., Batalov S., et al,. (2004) A gene atlas of the mouse and human protein-encoding transcriptomes. Proc. Natl Acad. Sci. USA 101, 6062-6067.
214. Suen I. S., Rhodes J. N., Christy M., McEwen B., Gray D. M., and, Mitas M., (1999) Structural properties of Friedreich's ataxia d(GAA) repeats. Biochim. Biophys. Acta 1444, 14-24.
215. Sugden M. C., Caton P. W., and, Holness M. J., (2010) PPAR control: it's SIRTainly as easy as PGC. J. Endocrinol. 204, 93-104.
216. Sun Y., Jiang X., Xu Y., Ayrapetov M. K., Moreau L. A., Whetstine J. R., and, Price B. D., (2009) Histone H3 methylation links DNA damage detection to activation of the tumour suppressor Tip60. Nat. Cell Biol. 11, 1376-1382.
217. Takai D., and, Jones P. A., (2002) Comprehensive analysis of CpG islands in human chromosomes 21 and 22. Proc. Natl Acad. Sci. USA 99, 3740-3745.
218. Tartof K. D., Hobbs C., and, Jones M., (1984) A structural basis for variegating position effects. Cell 37, 869-878.
219. Tartof K. D., Bishop C., Jones M., Hobbs C. A., and, Locke J., (1989) Towards an understanding of position effect variegation. Dev. Genet. 10, 162-176.
220. Ting D. T., Lipson D., Paul S., et al,. (2011) Aberrant overexpression of satellite repeats in pancreatic and other epithelial cancers. Science 331, 593-596.
221. Tomilin N. V., (1999) Control of genes by mammalian retroposons. Int. Rev. Cytol. 186, 1-48.
222. Tourtellotte W. G., and, Milbrandt J., (1998) Sensory ataxia and muscle spindle agenesis in mice lacking the transcription factor Egr3. Nat. Genet. 20, 87-91.
223. Tous C., and, Aguilera A., (2007) Impairment of transcription elongation by R-loops in vitro. Biochem. Biophys. Res. Commun. 360, 428-432.
224. Tschiersch B., Hofmann A., Krauss V., Dorn R., Korge G., and, Reuter G., (1994) The protein encoded by the Drosophila position-effect variegation suppressor gene Su(var)3-9 combines domains of antagonistic regulators of homeotic gene complexes. EMBO J. 13, 3822-3831.
225. Urdinguio R. G., Sanchez-Mut J. V., and, Esteller M., (2009) Epigenetic mechanisms in neurological diseases: genes, syndromes, and therapies. Lancet Neurol. 8, 1056-1072.
226. Vermeulen M., Mulder K. W., Denissov S., Pijnappel W. W., van Schaik F. M., Varier R. A., Baltissen M. P., Stunnenberg H. G., Mann M., and, Timmers H. T., (2007) Selective anchoring of TFIID to nucleosomes by trimethylation of histone H3 lysine 4. Cell 131, 58-69.
227. Volpe T. A., Kidner C., Hall I. M., Teng G., Grewal S. I., and, Martienssen R. A., (2002) Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science 297, 1833-1837.
228. Walhout A. J., Gubbels J. M., Bernards R., van der Vliet P. C., and, Timmers H. T., (1997) c-Myc/Max heterodimers bind cooperatively to the E-box sequences located in the first intron of the rat ornithine decarboxylase (ODC) gene. Nucleic Acids Res. 25, 1493-1501.
229. Wang Y. H., and, Griffith J., (1995) Expanded CTG triplet blocks from the myotonic dystrophy gene create the strongest known natural nucleosome positioning elements. Genomics 25, 570-573.
230. Wang Y. H., Amirhaeri S., Kang S., Wells R. D., and, Griffith J. D., (1994) Preferential nucleosome assembly at DNA triplet repeats from the myotonic dystrophy gene. Science 265, 669-671.
231. Wang H., Wang L., Erdjument-Bromage H., Vidal M., Tempst P., Jones R. S., and, Zhang Y., (2004) Role of histone H2A ubiquitination in Polycomb silencing. Nature 431, 873-878.
232. Wang F., Koyama N., Nishida H., Haraguchi T., Reith W., and, Tsukamoto T., (2006) The assembly and maintenance of heterochromatin initiated by transgene repeats are independent of the RNA interference pathway in mammalian cells. Mol. Cell. Biol. 26, 4028-4040.
233. Wang Z., Zang C., Rosenfeld J. A., et al,. (2008) Combinatorial patterns of histone acetylations and methylations in the human genome. Nat. Genet. 40, 897-903.
234. Witcher M., and, Emerson B. M., (2009) Epigenetic silencing of the p16(INK4a) tumor suppressor is associated with loss of CTCF binding and a chromatin boundary. Mol. Cell 34, 271-284.
235. Wu Z., Puigserver P., Andersson U., et al,. (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98, 115-124.
236. Wutz A., and, Jaenisch R., (2000) A shift from reversible to irreversible X inactivation is triggered during ES cell differentiation. Mol. Cell 5, 695-705.
237. Xiao T., Hall H., Kizer K. O., Shibata Y., Hall M. C., Borchers C. H., and, Strahl B. D., (2003) Phosphorylation of RNA polymerase II CTD regulates H3 methylation in yeast. Genes Dev. 17, 654-663.
238. Xu C., Soragni E., Chou C. J., Herman D., Plasterer H. L., Rusche J. R., and, Gottesfeld J. M., (2009) Chemical probes identify a role for histone deacetylase 3 in Friedreich's ataxia gene silencing. Chem. Biol. 16, 980-989.
239. Yang N., Zhang L., Zhang Y., and, Kazazian H. H., Jr, (2003) An important role for RUNX3 in human L1 transcription and retrotransposition. Nucleic Acids Res. 31, 4929-4940.
240. Yoder J. A., Walsh C. P., and, Bestor T. H., (1997) Cytosine methylation and the ecology of intragenomic parasites. Trends Genet. 13, 335-340.
241. Yu W., Gius D., Onyango P., Muldoon-Jacobs K., Karp J., Feinberg A. P., and, Cui H., (2008) Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA. Nature 451, 202-206.
242. Zarebski M., Wiernasz E., and, Dobrucki J. W., (2009) Recruitment of heterochromatin protein 1 to DNA repair sites. Cytometry A 75, 619-625.
243. Zhou Y. H., Zheng J. B., Gu X., Saunders G. F., and, Yung W. K., (2002) Novel PAX6 binding sites in the human genome and the role of repetitive elements in the evolution of gene regulation. Genome Res. 12, 1716-1722.
244. Zhu Q., Pao G. M., Huynh A. M., Suh H., Tonnu N., Nederlof P. M., Gage F. H., and, Verma I. M., (2011) BRCA1 tumour suppression occurs via heterochromatin-mediated silencing. Nature 477, 179-184.
245. Zuckerkandl E., (1974) A possible role of "inert" heterochromatin in cell differentiation. Action of and competition for "locking" molecules. Biochimie 56, 937-954.