Epigenetic changes and non-coding expanded repeats

Neurobiology of Disease

Volumn 39, Issue 1, 2010, Pages 21-27

  Nakamori, Masayuki ^a   Thornton, Charles ^a  

^a UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

Author keywords

Epigenetics; Fragile X syndrome; Friedreich ataxia; MBNL; Myotonic dystrophy; RNA dominance; Trinucleotide repeat

Indexed keywords

BINDING PROTEIN; BML 210; FRAGILE X MENTAL RETARDATION PROTEIN; FRATAXIN; HISTONE DEACETYLASE INHIBITOR; MUSCLEBLIND 1; UNCLASSIFIED DRUG;

5' UNTRANSLATED REGION; DNA METHYLATION; EPIGENETICS; FRAGILE X SYNDROME; FRIEDREICH ATAXIA; GENE EXPRESSION; GENE LOCATION; GENE MUTATION; GENE SILENCING; HUMAN; MENTAL DEFICIENCY; PHENOTYPE; PRIORITY JOURNAL; REGULATORY MECHANISM; REVIEW; TANDEM REPEAT;

ANIMALS; CHROMOSOME DISORDERS; EPIGENESIS, GENETIC; HEREDODEGENERATIVE DISORDERS, NERVOUS SYSTEM; HUMANS; MUTATION; REPETITIVE SEQUENCES, NUCLEIC ACID;

EID: 77952889125     PISSN: 09699961     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.nbd.2010.02.004     Document Type: Review

References (113)

1. Al-Mahdawi S., et al. The Friedreich ataxia GAA repeat expansion mutation induces comparable epigenetic changes in human and transgenic mouse brain and heart tissues. Hum. Mol. Genet. 2008, 17:735-746.
2. Amack J.D., et al. Cis and trans effects of the myotonic dystrophy (DM) mutation in a cell culture model. Hum. Mol. Genet. 1999, 8:1975-1984.
3. Bauer P.O., Nukina N. The pathogenic mechanisms of polyglutamine diseases and current therapeutic strategies. J. Neurochem. 2009, 110:1737-1765.
4. Bear M.F., et al. The mGluR theory of fragile X mental retardation. Trends Neurosci. 2004, 27:370-377.
5. Bidichandani S.I., et al. The GAA triplet-repeat expansion in Friedreich ataxia interferes with transcription and may be associated with an unusual DNA structure. Am. J. Hum. Genet. 1998, 62:111-121.
6. Brook J.D., et al. Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3Ž end of a transcript encoding a protein kinase family member. Cell 1992, 68:799-808.
7. Campuzano V., et al. Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 1996, 271:1423-1427.
8. Campuzano V., et al. Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes. Hum. Mol. Genet. 1997, 6:1771-1780.
9. Charlet-B N., et al. Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing. Mol. Cell 2002, 10:45-53.
10. Cho D.H., et al. Antisense transcription and heterochromatin at the DM1 CTG repeats are constrained by CTCF. Mol. Cell 2005, 20:483-489.
11. Coffee B., et al. Acetylated histones are associated with FMR1 in normal but not fragile X-syndrome cells. Nat. Genet. 1999, 22:98-101.
12. Coffee B., et al. Histone modifications depict an aberrantly heterochromatinized FMR1 gene in fragile x syndrome. Am. J. Hum. Genet. 2002, 71:923-932.
13. Dansithong W., et al. MBNL1 is the primary determinant of focus formation and aberrant insulin receptor splicing in DM1. J. Biol. Chem. 2005, 280:5773-5780.
14. Darnell J.C., et al. Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function. Cell 2001, 107:489-499.
15. Davis B.M., et al. Expansion of a CUG trinucleotide repeat in the 3Ž untranslated region of myotonic dystrophy protein kinase transcripts results in nuclear retention of transcripts. Proc. Natl. Acad. Sci. USA 1997, 94:7388-7393.
16. De Biase I., et al. Epigenetic silencing in Friedreich ataxia is associated with depletion of CTCF (CCCTC-binding factor) and antisense transcription. PLoS ONE 2009, 4:e7914.
17. De Boulle K., et al. A point mutation in the FMR-1 gene associated with fragile X mental retardation. Nat. Genet. 1993, 3:31-35.
18. de Haro M., et al. MBNL1 and CUGBP1 modify expanded CUG-induced toxicity in a Drosophila model of myotonic dystrophy type 1. Hum. Mol. Genet. 2006, 15:2138-2145.
19. D'Hulst C., Kooy R.F. Fragile X syndrome: from molecular genetics to therapy. J. Med. Genet. 2009, 46:577-584.
20. Di Prospero N.A., Fischbeck K.H. Therapeutics development for triplet repeat expansion diseases. Nat. Rev. Genet. 2005, 6:756-765.
21. Du H., et al. Aberrant alternative splicing and extracellular matrix gene expression in mouse models of myotonic dystrophy. Nat. Struct. Mol. Biol. 2010, 17:187-193.
22. Fardaei M., et al. Three proteins, MBNL, MBLL and MBXL, co-localize in vivo with nuclear foci of expanded-repeat transcripts in DM1 and DM2 cells. Hum. Mol. Genet. 2002, 11:805-814.
23. Feng Y., et al. Translational suppression by trinucleotide repeat expansion at FMR1. Science 1995, 268:731-734.
24. Filippova G.N., et al. CTCF-binding sites flank CTG/CAG repeats and form a methylation-sensitive insulator at the DM1 locus. Nat. Genet. 2001, 28:335-343.
25. Filla A., et al. The relationship between trinucleotide (GAA) repeat length and clinical features in Friedreich ataxia. Am. J. Hum. Genet. 1996, 59:554-560.
26. Furling D., et al. Viral vector producing antisense RNA restores myotonic dystrophy myoblast functions. Gene Ther. 2003, 10:795-802.
27. Garber K.B., et al. Fragile X syndrome. Eur. J. Hum. Genet. 2008, 16:666-672.
28. Gareiss P.C., et al. Dynamic combinatorial selection of molecules capable of inhibiting the (CUG) repeat RNA-MBNL1 interaction in vitro: discovery of lead compounds targeting myotonic dystrophy (DM1). J. Am. Chem. Soc. 2008, 130:16254-16261.
29. Gatchel J.R., Zoghbi H.Y. Diseases of unstable repeat expansion: mechanisms and common principles. Nat. Rev. Genet. 2005, 6:743-755.
30. Gedeon A.K., et al. Fragile X syndrome without CCG amplification has an FMR1 deletion. Nat. Genet. 1992, 1:341-344.
31. Gomes-Pereira M., Monckton D.G. Chemically induced increases and decreases in the rate of expansion of a CAG*CTG triplet repeat. Nucleic Acids Res. 2004, 32:2865-2872.
32. Grabczyk E., Usdin K. 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. 2000, 28:2815-2822.
33. Greco C.M., et al. Neuronal intranuclear inclusions in a new cerebellar tremor/ataxia syndrome among fragile X carriers. Brain 2002, 125:1760-1771.
34. Greene E., et al. Repeat-induced epigenetic changes in intron 1 of the frataxin gene and its consequences in Friedreich ataxia. Nucleic Acids Res. 2007, 35:3383-3390.
35. Hagerman P.J., Hagerman R.J. The fragile-X premutation: a maturing perspective. Am. J. Hum. Genet. 2004, 74:805-816.
36. Hagerman R.J., et al. Intention tremor, parkinsonism, and generalized brain atrophy in male carriers of fragile X. Neurology 2001, 57:127-130.
37. Hamshere M.G., et al. Transcriptional abnormality in myotonic dystrophy affects DMPK but not neighboring genes. Proc. Natl. Acad. Sci. USA 1997, 94:7394-7399.
38. Harper P.S. Myotonic Dystrophy 2001, W.B. Saunders Company, London.
39. Herman D., et al. Histone deacetylase inhibitors reverse gene silencing in Friedreich's ataxia. Nat. Chem. Biol. 2006, 2:551-558.
40. Ho T.H., et al. Muscleblind proteins regulate alternative splicing. EMBO J. 2004, 23:3103-3112.
41. Ho T.H., et al. Transgenic mice expressing CUG-BP1 reproduce splicing mis-regulation observed in myotonic dystrophy. Hum. Mol. Genet. 2005, 14:1539-1547.
42. Huber K.M., et al. Altered synaptic plasticity in a mouse model of fragile X mental retardation. Proc. Natl. Acad. Sci. USA 2002, 99:7746-7750.
43. Hunter A., et al. The correlation of age of onset with CTG trinucleotide repeat amplification in myotonic dystrophy. J. Med. Genet. 1992, 29:774-779.
44. Jacquemont S., et al. Fragile X premutation tremor/ataxia syndrome: molecular, clinical, and neuroimaging correlates. Am. J. Hum. Genet. 2003, 72:869-878.
45. Jacquemont S., et al. Fragile-X syndrome and fragile X-associated tremor/ataxia syndrome: two faces of FMR1. Lancet Neurol. 2007, 6:45-55.
46. Jansen G., et al. Abnormal myotonic dystrophy protein kinase levels produce only mild myopathy in mice. Nat. Genet. 1996, 13:316-324.
47. Jiang H., et al. Myotonic dystrophy type 1 associated with nuclear foci of mutant RNA, sequestration of muscleblind proteins, and deregulated alternative splicing in neurons. Hum. Mol. Genet. 2004, 13:3079-3088.
48. Jin P., et al. RNA-mediated neurodegeneration caused by the fragile X premutation rCGG repeats in Drosophila. Neuron 2003, 39:739-747.
49. Jin P., et al. Pur alpha binds to rCGG repeats and modulates repeat-mediated neurodegeneration in a Drosophila model of fragile X tremor/ataxia syndrome. Neuron 2007, 55:556-564.
50. Kanadia R.N., et al. A muscleblind knockout model for myotonic dystrophy. Science 2003, 302:1978-1980.
51. Kanadia R.N., et al. Developmental expression of mouse muscleblind genes Mbnl1, Mbnl2 and Mbnl3. Gene Expr. Patterns 2003, 3:459-462.
52. Kanadia R.N., et al. Reversal of RNA missplicing and myotonia after muscleblind overexpression in a mouse poly(CUG) model for myotonic dystrophy. Proc. Natl. Acad. Sci. USA 2006, 103:11748-11753.
53. Kenneson A., et al. Reduced FMRP and increased FMR1 transcription is proportionally associated with CGG repeat number in intermediate-length and premutation carriers. Hum. Mol. Genet. 2001, 10:1449-1454.
54. Klesert T.R., et al. Trinucleotide repeat expansion at the myotonic dystrophy locus reduces expression of the DMAHP gene. Nat. Genet. 1997, 16:402-406.
55. Klesert T.R., et al. Mice deficient in Six5 develop cataracts: implications for myotonic dystrophy. Nat. Genet. 2000, 25:105-109.
56. Krahe R., et al. Effect of myotonic dystrophy trinucleotide repeat expansion on DMPK transcription and processing. Genomics 1995, 28:1-14.
57. Kuyumcu-Martinez N.M., et al. Increased steady-state levels of CUGBP1 in myotonic dystrophy 1 are due to PKC-mediated hyperphosphorylation. Mol. Cell 2007, 28:68-78.
58. Ladd P.D., et al. An antisense transcript spanning the CGG repeat region of FMR1 is upregulated in premutation carriers but silenced in full mutation individuals. Hum. Mol. Genet. 2007, 16:3174-3187.
59. Langlois M.A., et al. Hammerhead ribozyme-mediated destruction of nuclear foci in myotonic dystrophy myoblasts. Mol. Ther. 2003, 7:670-680.
60. Langlois M.A., et al. Cytoplasmic and nuclear retained DMPK mRNAs are targets for RNA interference in myotonic dystrophy cells. J. Biol. Chem. 2005, 280:16949-16954.
61. Lin X., et al. Failure of MBNL1-dependent postnatal splicing transitions in myotonic dystrophy. Hum. Mol. Genet. 2006, 15:2087-2097.
62. Liquori C.L., et al. Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9. Science 2001, 293:864-867.
63. Lueck J.D., et al. Muscle chloride channel dysfunction in two mouse models of myotonic dystrophy. J. Gen. Physiol. 2007, 129:79-94.
64. Mankodi A., et al. Myotonic dystrophy in transgenic mice expressing an expanded CUG repeat. Science 2000, 289:1769-1773.
65. Mankodi A., et al. Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy. Mol. Cell 2002, 35-44.
66. Margolis J.M., et al. DM2 intronic expansions: evidence for CCUG accumulation without flanking sequence or effects on ZNF9 mRNA processing or protein expression. Hum. Mol. Genet. 2006, 15:1808-1815.
67. Martens J.H., et al. The profile of repeat-associated histone lysine methylation states in the mouse epigenome. EMBO J. 2005, 24:800-812.
68. Miller J.W., et al. Recruitment of human muscleblind proteins to (CUG)(n) expansions associated with myotonic dystrophy. EMBO J. 2000, 19:4439-4448.
69. Mulders S.A., et al. Triplet-repeat oligonucleotide-mediated reversal of RNA toxicity in myotonic dystrophy. Proc. Natl. Acad. Sci. USA 2009, 106:13915-13920.
70. Nichol K., Pearson C.E. CpG methylation modifies the genetic stability of cloned repeat sequences. Genome Res. 2002, 12:1246-1256.
71. Orengo J.P., et al. Expanded CTG repeats within the DMPK 3Ž UTR causes severe skeletal muscle wasting in an inducible mouse model for myotonic dystrophy. Proc. Natl. Acad. Sci. USA 2008, 105:2646-2651.
72. Orr H.T., Zoghbi H.Y. Trinucleotide repeat disorders. Annu. Rev. Neurosci. 2007, 30:575-621.
73. Osborne R.J., et al. Transcriptional and post-transcriptional impact of toxic RNA in myotonic dystrophy. Hum. Mol. Genet. 2009, 18:1471-1481.
74. Otten A.D., Tapscott S.J. Triplet repeat expansion in myotonic dystrophy alters the adjacent chromatin structure. Proc. Natl. Acad. Sci. USA 1995, 92:5465-5469.
75. Pandolfo M. Friedreich ataxia. Arch. Neurol. 2008, 65:1296-1303.
76. Pearson C.E., et al. Repeat instability: mechanisms of dynamic mutations. Nat. Rev. Genet. 2005, 6:729-742.
77. Philips A.V., et al. Disruption of splicing regulated by a CUG-binding protein in myotonic dystrophy. Science 1998, 280:737-741.
78. Pieretti M., et al. Absence of expression of the FMR-1 gene in fragile X syndrome. Cell 1991, 66:817-822.
79. Pietrobono R., et al. Quantitative analysis of DNA demethylation and transcriptional reactivation of the FMR1 gene in fragile X cells treated with 5-azadeoxycytidine. Nucleic Acids Res. 2002, 30:3278-3285.
80. Pietrobono R., et al. Molecular dissection of the events leading to inactivation of the FMR1 gene. Hum. Mol. Genet. 2005, 14:267-277.
81. Pushechnikov A., et al. Rational design of ligands targeting triplet repeating transcripts that cause RNA dominant disease: application to myotonic muscular dystrophy type 1 and spinocerebellar ataxia type 3. J. Am. Chem. Soc. 2009, 131:9767-9779.
82. Rai M., et al. HDAC inhibitors correct frataxin deficiency in a Friedreich ataxia mouse model. PLoS ONE 2008, 3:e1958.
83. Reddy S., et al. Mice lacking the myotonic dystrophy protein kinase develop a late onset progressive myopathy. Nat. Genet. 1996, 13:325-334.
84. Sakamoto N., et al. Sticky DNA: self-association properties of long GAA.TTC repeats in R.R.Y triplex structures from Friedreich's ataxia. Mol. Cell 1999, 3:465-475.
85. Sarkar P.S., et al. Heterozygous loss of Six5 in mice is sufficient to cause ocular cataracts. Nat. Genet. 2000, 25:110-114.
86. Saveliev A., et al. DNA triplet repeats mediate heterochromatin-protein-1-sensitive variegated gene silencing. Nature 2003, 422:909-913.
87. Savkur R.S., et al. Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy. Nat. Genet. 2001, 29:40-47.
88. Seznec H., et al. Mice transgenic for the human myotonic dystrophy region with expanded CTG repeats display muscular and brain abnormalities. Hum. Mol. Genet. 2001, 10:2717-2726.
89. Shao J., Diamond M.I. Polyglutamine diseases: emerging concepts in pathogenesis and therapy. Hum. Mol. Genet. 2007, 16(Spec No. 2):R115-R123.
90. Smith K.P., et al. Defining early steps in mRNA transport: mutant mRNA in myotonic dystrophy type I is blocked at entry into SC-35 domains. J. Cell Biol. 2007, 178:951-964.
91. Summerton J., Weller D. Morpholino antisense oligomers: design, preparation, and properties. Antisense Nucleic Acid Drug Dev. 1997, 7:187-195.
92. Sutcliffe J.S., et al. DNA methylation represses FMR-1 transcription in fragile X syndrome. Hum. Mol. Genet. 1992, 1:397-400.
93. Taneja K.L., et al. Foci of trinucleotide repeat transcripts in nuclei of myotonic dystrophy cells and tissues. J. Cell Biol. 1995, 128:995-1002.
94. Tassone F., et al. Elevated levels of FMR1 mRNA in carrier males: a new mechanism of involvement in the fragile-X syndrome. Am. J. Hum. Genet. 2000, 66:6-15.
95. Tassone F., et al. Intranuclear inclusions in neural cells with premutation alleles in fragile X associated tremor/ataxia syndrome. J. Med. Genet. 2004, 41:e43.
96. Tassone F., et al. FMR1 RNA within the intranuclear inclusions of fragile X-associated tremor/ataxia syndrome (FXTAS). RNA Biol. 2004, 1:103-105.
97. Taylor A.K., et al. Tissue heterogeneity of the FMR1 mutation in a high-functioning male with fragile X syndrome. Am. J. Med. Genet. 1999, 84:233-239.
98. Thornton C.A., et al. Expansion of the myotonic dystrophy CTG repeat reduces expression of the flanking DMAHP gene. Nat. Genet. 1997, 16:407-409.
99. Timchenko N.A., et al. Molecular basis for impaired muscle differentiation in myotonic dystrophy. Mol. Cell. Biol. 2001, 21:6927-6938.
100. Timchenko N.A., et al. Overexpression of CUG triplet repeat-binding protein, CUGBP1, in mice inhibits myogenesis. J. Biol. Chem. 2004, 279:13129-13139.
101. Tsilfidis C., et al. Correlation between CTG trinucleotide repeat length and frequency of severe congenital myotonic dystrophy. Nat. Genet. 1992, 1:192-195.
102. Verkerk A.J., et al. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 1991, 65:905-914.
103. Wang G.S., et al. Elevation of RNA-binding protein CUGBP1 is an early event in an inducible heart-specific mouse model of myotonic dystrophy. J. Clin. Invest. 2007, 117:2802-2811.
104. Warf M.B., Berglund J.A. MBNL binds similar RNA structures in the CUG repeats of myotonic dystrophy and its pre-mRNA substrate cardiac troponin T. RNA 2007, 13:2238-2251.
105. Warf M.B., et al. Pentamidine reverses the splicing defects associated with myotonic dystrophy. Proc. Natl. Acad. Sci. USA 2009, 106:18551-18556.
106. Wheeler T.M., et al. Reversal of RNA dominance by displacement of protein sequestered on triplet repeat RNA. Science 2009, 325:336-339.
107. Willemsen R., et al. The FMR1 CGG repeat mouse displays ubiquitin-positive intranuclear neuronal inclusions; implications for the cerebellar tremor/ataxia syndrome. Hum. Mol. Genet. 2003, 12:949-959.
108. Williams A.J., Paulson H.L. Polyglutamine neurodegeneration: protein misfolding revisited. Trends Neurosci. 2008, 31:521-528.
109. Wohrle D., et al. Mitotic stability of fragile X mutations in differentiated cells indicates early post-conceptional trinucleotide repeat expansion. Nat. Genet. 1993, 4:140-142.
110. Wohrle D., et al. Unusual mutations in high functioning fragile X males: apparent instability of expanded unmethylated CGG repeats. J. Med.Genet. 1998, 35:103-111.
111. Xu C., et al. Chemical probes identify a role for histone deacetylase 3 in Friedreich's ataxia gene silencing. Chem. Biol. 2009, 16:980-989.
112. Yang Z., et al. Replication inhibitors modulate instability of an expanded trinucleotide repeat at the myotonic dystrophy type 1 disease locus in human cells. Am. J. Hum. Genet. 2003, 73:1092-1105.
113. Yuan Y., et al. Muscleblind-like 1 interacts with RNA hairpins in splicing target and pathogenic RNAs. Nucleic Acids Res. 2007, 35:5474-5486.