Transcription defects induced by repeat expansion: Fragile X syndrome, FRAXE mental retardation, progressive myoclonus epilepsy type 1, and Friedreich ataxia

Cytogenetic and Genome Research

Volumn 100, Issue 1-4, 2003, Pages 65-76

  Greene, E ^a   Handa, V ^a   Kumari, D ^a   Usdin, K ^a,b  

^a NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES   (United States)

^b NATIONAL INSTITUTES OF HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DISEASE ASSOCIATION; DISEASE COURSE; DOWN REGULATION; FRAGILE X SYNDROME; FRAXE MENTAL RETARDATION; FRIEDREICH ATAXIA; GENE SILENCING; GENETIC TRANSCRIPTION; HUMAN; MENTAL DEFICIENCY; METHYLATION; MYOCLONUS EPILEPSY; PRIORITY JOURNAL; PROMOTER REGION; REVIEW;

BASE SEQUENCE; DNA; FRAGILE X SYNDROME; FRIEDREICH ATAXIA; GENE EXPRESSION REGULATION; HUMANS; MENTAL RETARDATION, X-LINKED; MODELS, BIOLOGICAL; MUTATION; MYOCLONIC EPILEPSIES, PROGRESSIVE; NUCLEIC ACID CONFORMATION; TRANSCRIPTION, GENETIC; TRINUCLEOTIDE REPEAT EXPANSION;

ATAXIA;

EID: 0344962401     PISSN: 14248581     EISSN: None     Source Type: Journal    
DOI: 10.1159/000072839     Document Type: Review

References (136)

1. Alakurtti K, Virtaneva K, Joensuu T, Palvimo JJ, Lehesjoki AE: Characterization of the cystatin B gene promoter harboring the dodecamer repeat expanded in progressive myoclonus epilepsy, EPM1. Gene 242:65-73 (2000).
2. Allingham-Hawkins DJ, Babul-Hirji R, Chitayat D, Holden JJ, Yang KT, Lee C, Hudson R, Gorwill H, Nolin SL, Glicksman A, et al: Fragile X premutation is a significant risk factor for premature ovarian failure: the International Collaborative POF in Fragile X study - preliminary data. Am J med Genet 83: 322-325 (1999).
3. Allshire R: Molecular Biology: RNAi and heterochromatin - a hushed-up affair. Science 297:1818-1819 (2002).
4. Ashley CT Jr., Wilkinson KD, Reines D, Warren ST: FMR1 protein: conserved RNP family domains and selective RNA binding. Science 262:563-566 (1993a).
5. Ashley CT, Sutcliffe JS, Kunst CB, Leiner HA, Eichler EE, Nelson DL, Warren ST: Human and murine FMR-1: alternative splicing and translational initiation downstream of the CGG-repeat. Nature Genet 4: 244-251 (1993b).
6. Banks EB, Crish JF, Welter JF, Eckert RL: Characterization of human involucrin promoter distal regulatory region transcriptional activator elements-a role for Sp1 and AP1 binding sites. Biochem J 331:61-68 (1998).
7. Bidichandani SI, Ashizawa T, Patel PI: 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 (1998).
8. Braun K, Segal M: FMRP involvement in formation of synapses among cultured hippocampal neurons. Cereb Cortex 10:1045-1052 (2000).
9. Brown V, Jin P, Ceman S, Darnell JC, O'Donnell WT, Tenenbaum SA, Jin X, Feng Y, Wilkinson KD, Keene JD, et al: Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome. Cell 107:477-487 (2001).
10. Buj-Bello A, Furling D, Tronchere H, Laporte J, Lerouge T, Butler-Browne GS, Mandel JL: Muscle-specific alternative splicing of myotubularin-related 1 gene is impaired in DM1 muscle cells. Hum molec Genet 11:2297-2307 (2002).
11. Burman RW, Yates PA, Green LD, Jacky PB, Turker MS, Popovich BW: Hypomethylation of an expanded FMR1 allele is not associated with a global DNA methylation defect. Am J hum Genet 65:1375-1386 (1999).
12. Campuzano V, Montermini L, Molto MD, Pianese L, Cossee M, Cavalcanti F, Monros E, Rodius F, Duclos F, Monticelli A, et al: Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 271:1423-1427 (1996).
13. Cao YX, Jean JC, Williams MC: Cytosine methylation of an Sp1 site contributes to organ-specific and cell-specific regulation of expression of the lung epithelial gene t1 alpha. Biochem J 350:883-890 (2000).
14. Caudy AA, Myers M, Hannon GJ, Hammond SM: Fragile X-related protein and VIG associate with the RNA interference machinery. Genes Dev 16: 2491-2496 (2002).
15. Chakrabarti L, Bristulf J, Foss GS, Davies KE: Expression of the murine homologue of FMR2 in mouse brain and during development. Hum molec Genet 7:441-448 (1998).
16. Chen OS, Hemenway S, Kaplan J: Inhibition of Fe-S cluster biosynthesis decreases mitochondrial iron export: Evidence that Yfh1p affects Fe-S cluster synthesis. Proc natl Acad Sci, USA (2002).
17. Chen X, Mariappan SV, Catasti P, Ratliff R, Moyzis RK, Laayoun A, Smith SS, Bradbury EM, Gupta G: Hairpins are formed by the single DNA strands of the fragile X triplet repeats: structure and biological implications. Proc natl Acad Sci, USA 92: 5199-5203 (1995).
18. Chen X, Mariappan SV, Moyzis RK, Bradbury EM, Gupta G: Hairpin induced slippage and hypermethylation of the fragile X DNA triplets. J Biomol Struct Dyn 15:745-756 (1998).
19. Chiurazzi P, Pomponi MG, Willemsen R, Oostra BA, Neri G: In vitro reactivation of the FMR1 gene involved in fragile X syndrome. Hum molec Genet 7:109-113 (1998).
20. Coffee B, Zhang F, Warren ST, Reines D: Acetylated histones are associated with FMR1 in normal but not fragile X-syndrome cells. Nature Genet 22:98-101 (1999).
21. Coffee B, Zhang F, Ceman S, Warren ST, Reines D: Histone modifications depict an aberrantly heterochromatinized FMR1 gene in fragile X syndrome. Am J hum Genet 71:(2002).
22. Cook T, Gebelein B, Belal M, Mesa K, Urrutia R: Three conserved transcriptional repressor domains are a defining feature of the TIEG subfamily of Sp1-like zinc finger proteins. J biol Chem 274:29500-29504 (1999).
23. Cossee M, Puccio H, Gansmuller A, Koutnikova H, Dierich A, LeMeur M, Fischbeck K, Dolle P, Koenig M: Inactivation of the Friedreich ataxia mouse gene leads to early embryonic lethality without iron accumulation. Hum molec Genet 9:1219-1226 (2000).
24. D'Amato E, Kokaia Z, Nanobashvili A, Reeben M, Lehesjoki AE, Saarma M, Lindvall O: Seizures induce widespread upregulation of cystatin B, the gene mutated in progressive myoclonus epilepsy, in rat forebrain neurons. Eur J Neurosci 12:1687-1695 (2000).
25. Darnell JC, Jensen KB, Jin P, Brown V, Warren ST, Darnell RB: Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function. Cell 107:489-499 (2001).
26. De Boulle K, Verkerk AJ, Reyniers E, Vits L, Hendrickx J, Van Roy B, Van den Bos F, de Graaff E, Oostra BA, Willems PJ: A point mutation in the FMR-1 gene associated with fragile X mental retardation. Nature Genet 3:31-35 (1993).
27. Dennis K, Fan T, Geiman T, Yan Q, Muegge K: Lsh, a member of the SNF2 family, is required for genome-wide methylation. Genes Dev 15:2940-2944 (2001).
28. Di Giaimo R, Riccio M, Santi S, Galeotti C, Ambrosetti DC, Melli M: New insights into the molecular basis of progressive myoclonus epilepsy: a multi-protein complex with cystatin B. Hum molec Genet 11:2941-2950 (2002).
29. Dockendorff TC, Su HS, McBride SM, Yang Z, Choi CH, Siwicki KK, Sehgal A, Jongens TA: Drosophila lacking dfmr1 activity show defects in circadian output and fail to maintain courtship interest. Neuron 34:973-984 (2002).
30. Drouin R, Angers M, Dallaire N, Rose TM, Khandjian W, Rousseau F: Structural and functional characterization of the human FMR1 promoter reveals similarities with the hnRNP-A2 promoter region. Hum molec Genet 6:2051-2060 (1997).
31. Durr A, Cossee M, Agid Y, Campuzano V, Mignard C, Penet C, Mandel JL, Brice A, Koenig M: Clinical and genetic abnormalities in patients with Friedreich's ataxia. New Engl J Med 335:1169-1175 (1996).
32. Feng Y, Zhang F, Lokey LK, Chastain JL, Lakkis L, Eberhart D, Warren ST: Translational suppression by trinucleotide repeat expansion at FMR1. Science 268:731-734 (1995).
33. Feng Y, Absher D, Eberhart DE, Brown V, Malter HE, Warren ST: FMRP associates with polyribosomes as an mRNP, and the I304N mutation of severe fragile X syndrome abolishes this association. Mol Cell 1:109-118 (1997a).
34. Feng Y, Gutekunst CA, Eberhart DE, Yi H, Warren ST, Hersch SM: Fragile X mental retardation protein: nucleocytoplasmic shuttling and association with somatodendritic ribosomes. J Neurosci 17:1539-1547 (1997b).
35. Filla A, De Michele G, Cavalcanti F, Pianese L, Monti-celli A, Campanella G, Cocozza S: The relationship between trinucleotide (GAA) repeat length and clinical features in Friedreich ataxia. Am J hum Genet 59:554-560 (1996).
36. Foury F: Low iron concentration and aconitase deficiency in a yeast frataxin homologue deficient strain. FEBS Lett 456:281-284 (1999).
37. Fry M, Loeb LA: The fragile X syndrome d(CGG)n nucleotide repeats form a stable tetrahelical structure. Proc natl Acad Sci, USA 91:4950-4954 (1994).
38. Fu YH, Kuhl DP, Pizzuti A, Pieretti M, Sutcliffe JS, Richards S, Verkerk AJ, Holden JJ, Fenwick RG Jr., Warren ST, et al: Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. Cell 67:1047-1058 (1991).
39. Fuks F, Hurd PJ, Wolf D, Nan X, Bird AP, Kouzarides T: The methyl-CpG-binding protein MeCP2 links DNA methylation to histone methylation. J biol Chem (2002).
40. Gacy AM, Goellner GM, Spiro C, Chen X, Gupta G, Bradbury EM, Dyer RB, Mikesell MJ, Yao JZ, Johnson AJ, et al: GAA instability in Friedreich's Ataxia shares a common, DNA-directed and intraallelic mechanism with other trinucleotide diseases. Mol Cell 1:583-593 (1998).
41. Gecz J: The FMR2 gene, FRAXE and non-specific X-linked mental retardation: clinical and molecular aspects. Ann hum Genet 64:95-106 (2000a).
42. Gecz J: FMR3 is a novel gene associated with FRAXE CpG island and transcriptionally silent in FRAXE full mutations. J med Genet 37:782-784 (2000b).
43. Gecz J, Gedeon AK, Sutherland GR, Mulley JC: Identification of the gene FMR2, associated with FRAXE mental retardation. Nature Genet 13: 105-108 (1996).
44. Gecz J, Oostra BA, Hockey A, Carbonell P, Turner G, Haan EA, Sutherland GR, Mulley JC: FMR2 expression in families with FRAXE mental retardation. Hum molec Genet 6:435-441 (1997).
45. Grabczyk E, Fishman MC: A long purine-pyrimidine homopolymer acts as a transcriptional diode. J biol Chem 270:1791-1797 (1995).
46. Grabczyk E, Usdin K: Length dependent transcription attenuation in the Friedreich's ataxia triplet expansion mutation (GAA) via triple helix formation. FASEB J 11:1998 (1997).
47. Grabczyk E, Usdin K: Alleviating transcript insufficiency caused by Friedreich's ataxia triplet repeats. Nucl Acids Res 28:4930-4937 (2000a).
48. 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. Nucl Acids Res 28:2815-2822 (2000b).
49. Greco CM, Hagerman RJ, Tassone F, Chudley AE, Del Bigio MR, Jacquemont S, Leehey M, Hagerman PJ: Neuronal intranuclear inclusions in a new cerebellar tremor/ataxia syndrome among fragile X carriers. Brain 125:1760-1771 (2002).
50. Gu Y, Shen Y, Gibbs RA, Nelson DL: Identification of FMR2, a novel gene associated with the FRAXE CCG repeat and CpG island. Nature Genet 13: 109-113 (1996).
51. Gu Y, McIlwain KL, Weeber EJ, Yamagata T, Xu B, Antalffy BA, Reyes C, Yuva-Paylor L, Armstrong D, Zoghbi H, et al: Impaired conditioned fear and enhanced long-term potentiation in Fmr2 knockout mice. J Neurosci 22:2753-2763 (2002).
52. Hampel KJ, Ashley C, Lee JS: Kilobase-range communication between polypurine, polypyrimidine tracts in linear plasmids mediated by triplex formation: a braided knot between two linear duplexes. Biochemistry 33: 5674-5681 (1994).
53. Hanvey JC, Shimizu M, Wells RD: Intramolecular DNA triplexes in supercoiled plasmids. Proc natl Acad Sci, USA 85:6292-6296 (1988).
54. Hashem VI, Sinden RR: Chemotherapeutically induced deletion of expanded triplet repeats. Mutat Res 508:107-119 (2002).
55. Heard E, Rougeulle C, Arnaud D, Avner P, Allis CD, Spector DL: Methylation of histone H3 at Lys-9 is an early mark on the X chromosome during X inactivation. Cell 107:727-738 (2001).
56. Hillman MA, Gecz J: Fragile XE-associated familial mental retardation protein 2 (FMR2) acts as a potent transcription activator. J Hum Genet 46:251-259 (2001).
57. Hornstra IK, Nelson DL, Warren ST, Yang TP: High resolution methylation analysis of the FMR1 gene trinucleotide repeat region in fragile X syndrome. Hum molec Genet 2:1659-1665 (1993).
58. Huynen MA, Snel B, Bork P, Gibson TJ: The phylogenetic distribution of frataxin indicates a role in iron-sulfur cluster protein assembly. Hum molec Genet 10:2463-2468 (2001).
59. Inoue S, Shimoda M, Nishinokubi I, Siomi MC, Okamura M, Nakamura A, Kobayashi S, Ishida N, Siomi H: A role for the Drosophila fragile X-related gene in circadian output. Curr Biol 12:1331-1335 (2002).
60. Irwin SA, Galvez R, Greenough WT: Dendritic spine structural anomalies in fragile-X mental retardation syndrome. Cereb Cortex 10:1038-1044 (2000).
61. Ishizuka A, Siomi MC, Siomi H: A Drosophila fragile X protein interacts with components of RNAi and ribosomal proteins. Genes Dev 16:2497-2508 (2002).
62. Isnard R, Kalotka H, Durr A, Cossee M, Schmitt M, Pousset F, Thomas D, Brice A, Koenig M, Komajda M: Correlation between left ventricular hypertrophy and GAA trinucleotide repeat length in Friedreich's ataxia. Circulation 95:2247-2249 (1997).
63. Jeddeloh JA, Stokes TL, Richards EJ: Maintenance of genomic methylation requires a SWI2/SNF2-like protein. Nature Genet 22:94-97 (1999).
64. Jones L, Ratcliff F, Baulcombe DC: RNA-directed transcriptional gene silencing in plants can be inherited independently of the RNA trigger and requires Met1 for maintenance. Curr Biol 11:747-757 (2001).
65. Kaluzova M, Pastorekova S, Svastova E, Pastorek J, Stanbridge EJ, Kaluz S: Characterization of the MN/CA 9 promoter proximal region: a role for specificity protein (SP) and activator protein 1 (AP1) factors. Biochem J 359:669-677 (2001).
66. Kenneson A, Zhang F, Hagedorn CH, Warren ST: Reduced FMRP and increased FMR1 transcription is proportionally associated with CGG repeat number in intermediate-length and premutation carriers. Hum molec Genet 10:1449-1454 (2001).
67. Kettani A, Kumar RA, Patel DJ: Solution structure of a DNA quadruplex containing the fragile X syndrome triplet repeat. J molec Biol 254:638-656 (1995).
68. Khandjian EW, Bardoni B, Corbin F, Sittler A, Giroux S, Heitz D, Tremblay S, Pinset C, Montarras D, Rousseau F, et al: Novel isoforms of the fragile X related protein FXR1P are expressed during myogenesis. Hum molec Genet 7:2121-2128 (1998).
69. Kinne R, Saukko P, Jarvinen M, Lehesjoki AE: Reduced cystatin B activity correlates with enhanced cathepsin activity in progressive myoclonus epilepsy. Ann Med 34:380-385 (2002).
70. Kumari D, Usdin K: Interaction of the transcription factors USF1, USF2, and alpha -Pal/Nrf-1 with the FMR1 promoter. Implications for Fragile X mental retardation syndrome. J biol Chem 276:4357-4364 (2001).
71. Laayoun A, Smith SS: Methylation of slipped duplexes, snapbacks and cruciforms by human DNA(cytosine-5)methyltransferase. Nucl Acids Res 23:1584-1589 (1995).
72. Lafreniere RG, Rochefort DL, Chretien N, Rommens JM, Cochius JI, Kalviainen R, Nousiainen U, Patry G, Farrell K, Soderfeldt B, et al: Unstable insertion in the 5)flanking region of the cystatin B gene is the most common mutation in progressive myoclonus epilepsy type 1, EPM1. Nature Genet 15: 298-302 (1997).
73. Lalioti MD, Scott HS, Buresi C, Rossier C, Bottani A, Morris MA, Malafosse A, Antonarakis SE: Dodecamer repeat expansion in cystatin B gene in progressive myoclonus epilepsy. Nature 386:847-851 (1997).
74. Lalioti MD, Scott HS, Antonarakis SE: Altered spacing of promoter elements due to the dodecamer repeat expansion contributes to reduced expression of the cystatin B gene in EPM1. Hum molec Genet 8:1791-1798 (1999).
75. Lee JS, Ashley C, Hampel KJ, Bradley R, Scraba DG: A stable interaction between separated pyrimidine.purine tracts in circular DNA. J molec Biol 252:283-288 (1995).
76. Leehey MA, Hagerman RJ, Landau WM, Grigsby J, Tassone F, Hagerman PJ: Tremor/ataxia syndrome in fragile X carrier males. Mov Disord 17:744-745 (2002).
77. Lieuallen K, Pennacchio LA, Park M, Myers RM, Lennon GG: Cystatin B-deficient mice have increased expression of apoptosis and glial activation genes. Hum molec Genet 10:1867-1871 (2001).
78. Lindsay H, Adams RL: Spreading of methylation along DNA. Biochem J 320:473-478 (1996).
79. Lo Nigro C, Faravelli F, Cavani S, Perroni L, Novello P, Vitali M, Bricarelli FD, Grasso M: FRAXE mutation in a mentally retarded subject and in his phenotypically normal twin brother. Eur J hum Genet 8:157-162 (2000).
80. Loesch DZ, Huggins RM, Bui QM, Epstein JL, Taylor AK, Hagerman RJ: Effect of the deficits of fragile X mental retardation protein on cognitive status of fragile X males and females assessed by robust pedigree analysis. J Dev Behav Pediatr 23:416-423 (2002).
81. Lugenbeel KA, Peier AM, Carson NL, Chudley AE, Nelson DL: Intragenic loss of function mutations demonstrate the primary role of FMR1 in fragile X syndrome. Nature Genet 10:483-485 (1995).
82. Mancini DN, Singh SM, Archer TK, Rodenhiser DI: Site-specific DNA methylation in the neurofibromatosis (NF1) promoter interferes with binding of CREB and SP1 transcription factors. Oncogene 18:4108-4119 (1999).
83. n. Nucl Acids Res 24:784-792 (1996).
84. n with selective 15N4-labeled cytosine bases. J molec Biol 283:111-120 (1998).
85. McDaniel DO, Keats B, Vedanarayanan VV, Subramony SH: Sequence variation in GAA repeat expansions may cause differential phenotype display in Friedreich's ataxia. Mov Disord 16:1153-1158 (2001).
86. Mette MF, Aufsatz W, van der Winden J, Matzke MA, Matzke AJ: Transcriptional silencing and promoter methylation triggered by double-stranded RNA. EMBO J 19:5194-5201 (2000).
87. Mitas M, Yu A, Dill J, Haworth IS: The trinucleotide repeat sequence d(CGG)15 forms a heat-stable hairpin containing Gsyn. Ganti base pairs. Biochemistry 34:12803-12811 (1995).
88. Morales J, Hiesinger PR, Schroeder AJ, Kume K, Verstreken P, Jackson FR, Nelson DL, Hassan BA: Drosophila fragile X protein, DFXR, regulates neuronal morphology and function in the brain. Neuron 34:961-972 (2002).
89. Muhlenhoff U, Richhardt N, Ristow M, Kispal G, Lill R: The yeast frataxin homolog Yfh1p plays a specific role in the maturation of cellular Fe/S proteins. Hum molec Genet 11:2025-2036 (2002).
90. Murgia A, Polli R, Vinanzi C, Salis M, Drigo P, Artifoni L, Zacchello F: Amplification of the Xq28 FRAXE repeats: extreme phenotype variability? Am J med Genet 64:441-444 (1996).
91. Murray A, Webb J, Dennis N, Conway G, Morton N: Microdeletions in FMR2 may be a significant cause of premature ovarian failure. J med Genet 36:767-770 (1999).
92. n nucleotide repeats readily fold back to form unimolecular hairpin structures. J biol Chem 270:28970-28977 (1995).
93. Nishikura K: A short primer on RNAi: RNA-directed RNA polymerase acts as a key catalyst. Cell 107:415-418 (2001).
94. Ohshima K, Montermini L, Wells RD, Pandolfo M: 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 (1998).
95. Ohshima K, Sakamoto N, Labuda M, Poirier J, Moseley ML, Montermini L, Ranum LP, Wells RD, Pandolfo M: A nonpathogenic GAAGGA repeat in the Friedreich gene: implications for pathogenesis. Neurology 53:1854-1857 (1999).
96. Pandolfo M: Molecular basis of Friedreich ataxia. Mov Disord 16:815-821 (2001).
97. n. J Biomol Struct Dyn 19:307-313 (2001a).
98. n forms folded hairpin structures at physiological pH. J Biomol Struct Dyn 19:293-305 (2001b).
99. Patel PK, Bhavesh NS, Hosur RV: Cation-dependent conformational switches in d-TGGCGGC containing two triplet repeats of fragile X syndrome: NMR observations. Biochem biophys Res Commun 278:833-838 (2000).
100. Pennacchio LA, Lehesjoki AE, Stone NE, Willour VL, Virtaneva K, Miao J, D'Amato E, Ramirez L, Faham M, Koskiniemi M, et al: Mutations in the gene encoding cystatin B in progressive myoclonus epilepsy (EPM1). Science 271:1731-1734 (1996).
101. Philips AV, Timchenko LT, Cooper TA: Disruption of splicing regulated by a CUG-binding protein in myotonic dystrophy. Science 280:737-741 (1998).
102. Pieretti M, Zhang FP, Fu YH, Warren ST, Oostra BA, Caskey CT, Nelson DL: Absence of expression of the FMR-1 gene in fragile X syndrome. Cell 66:817-822 (1991).
103. Pietrobono R, Pomponi MG, Tabolacci E, Oostra B, Chiurazzi P, Neri G: Quantitative analysis of DNA demethylation and transcriptional reactivation of the FMR1 gene in fragile X cells treated with 5-azadeoxycytidine. Nucl Acids Res 30:3278-3285 (2002).
104. Puccio H, Simon D, Cossee M, Criqui-Filipe P, Tiziano F, Melki J, Hindelang C, Matyas R, Rustin P, Koenig M: Mouse models for Friedreich ataxia exhibit cardiomyopathy, sensory nerve defect and Fe-S enzyme deficiency followed by intramitochondrial iron deposits. Nature Genet 27:181-186 (2001).
105. Raca G, Siyanova E, Mirkin S: Janus effects of premutation size CGG repeats on gene expression. Am J hum Genet 67:2046 (2000).
106. Ranum LP, Day JW: Dominantly inherited, non-coding microsatellite expansion disorders. Curr Opin Genet Dev 12:266-271 (2002).
107. Razin A: CpG methylation, chromatin structure and gene silencing - a three-way connection. EMBO J 17:4905-4908 (1998).
108. Riccio M, Di Giaimo R, Pianetti S, Palmieri PP, Melli M, Santi S: Nuclear localization of cystatin B, the cathepsin inhibitor implicated in myoclonus epilepsy (EPM1). Exp Cell Res 262:84-94 (2001).
109. Saha T, Usdin K: Tetraplex formation by the progressive myoclonus epilepsy type-1 repeat: implications for instability in the repeat expansion diseases. FEBS Lett 491:184-187 (2001).
110. Sandberg G, Schalling M: Effect of in vitro promoter methylation and CGG repeat expansion on FMR-1 expression. Nucl Acids Res 25:2883-2887 (1997).
111. Sarkar PS, Brahmachari SK: Intramolecular triplex potential sequence within a gene down regulates its expression in vivo. Nucl Acids Res 20: 5713-5718 (1992).
112. Savkur RS, Philips AV, Cooper TA: Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy. Nature Genet 29:40-47 (2001).
113. Schaeffer C, Bardoni B, Mandel JL, Ehresmann B, Ehresmann C, Moine H: The fragile X mental retardation protein binds specifically to its mRNA via a purine quartet motif. EMBO J 20:4803-4813 (2001).
114. Schwemmle S, de Graaff E, Deissler H, Glaser D, Wohrle D, Kennerknecht I, Just W, Oostra BA, Dorfler W, Vogel W, et al: Characterization of FMR1 promoter elements by in vivo-footprinting analysis. Am J hum Genet 60:1354-1362 (1997).
115. Shannon P, Pennacchio LA, Houseweart MK, Minassian BA, Myers RM: Neuropathological changes in a mouse model of progressive myoclonus epilepsy: cystatin B deficiency and Unverricht-Lundborg disease. J Neuropathol Exp Neurol 61:1085-1091 (2002).
116. Siomi MC, Siomi H, Sauer WH, Srinivasan S, Nussbaum RL, Dreyfuss G: FXR1, an autosomal homolog of the fragile X mental retardation gene. EMBO J 14:2401-2408 (1995).
117. Smeets HJ, Smits AP, Verheij CE, Theelen JP, Willemsen R, van de Burgt I, Hoogeveen AT, Oosterwijk JC, Oostra BA: Normal phenotype in two brothers with a full FMR1 mutation. Hum molec Genet 4:2103-2108 (1995).
118. Sutcliffe JS, Nelson DL, Zhang F, Pieretti M, Caskey CT, Saxe D, Warren ST: DNA methylation represses FMR-1 transcription in fragile X syndrome. Hum molec Genet 1:397-400 (1992).
119. Tamaru H, Selker EU: A histone H3 methyltransferase controls DNA methylation in Neurospora crassa. Nature 414:277-283 (2001).
120. Tan SL, Katze MG: The emerging role of the interferon-induced PKR protein kinase as an apoptotic effector: a new face of death? J Interferon Cytokine Res 19:543-554 (1999).
121. Tassone F, Hagerman RJ, Loesch DZ, Lachiewicz A, Taylor AK, Hagerman PJ: Fragile X males with unmethylated, full mutation trinucleotide repeat expansions have elevated levels of FMR1 messenger RNA. Am J med Genet 94: 232-236 (2000a).
122. Tassone F, Hagerman RJ, Taylor AK, Gane LW, Godfrey TE, Hagerman PJ: Elevated levels of FMR1 mRNA in carrier males: a new mechanism of involvement in the fragile-X syndrome. Am J hum Genet 66:6-15 (2000b).
123. Tassone F, Hagerman RJ, Taylor AK, Hagerman PJ: A majority of fragile X males with methylated, full mutation alleles have significant levels of FMR1 messenger RNA. J med Genet 38:453-456 (2001).
124. Taylor JP, Fischbeck KH: Altered acetylation in polyglutamine disease: an opportunity for therapeutic intervention? Trends Mol Med 8:195-197 (2002).
125. Usdin K: NGG-triplet repeats form similar intrastrand structures: implications for the triplet expansion diseases. Nucl Acids Res 26:4078-4085 (1998).
126. Usdin K, Woodford KJ: CGG repeats associated with DNA instability and chromosome fragility form structures that block DNA synthesis in vitro. Nucl Acids Res 23:4202-4209 (1995).
127. Uzielli ML, Guarducci S, Lapi E, Cecconi A, Ricci U, Ricotti G, Biondi C, Scarselli B, Vieri F, Scarnato P, et al: Premature ovarian failure (POF) and fragile X premutation females: from POF to to fragile X carrier identification, from fragile X carrier diagnosis to POF association data. Am J med Genet 84:300-303 (1999).
128. Verkerk AJ, Pieretti M, Sutcliffe JS, Fu YH, Kuhl DP, Pizzuti A, Reiner O, Richards S, Victoria MF, Zhang FP, 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 65:905-914 (1991).
129. Vetcher AA, Napierala M, Iyer RR, Chastain PD, Griffith JD, Wells RD: Sticky DNA, a long GAA5G-AA5TTC triplex which is formed intramolecularly, in the sequence of intron 1 of the Frataxin gene. J biol Chem (2002).
130. Virtaneva K, D'Amato E, Miao J, Koskiniemi M, Norio R, Avanzini G, Franceschetti S, Michelucci R, Tassinari CA, Omer S, et al: Unstable minisatellite expansion causing recessively inherited myoclonus epilepsy, EPM1. Nature Genet 15:393-396 (1997).
131. Volpe TA, Kidner C, Hall IM, Teng G, Grewal SI, Martienssen RA: Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science 297:1833-1837 (2002).
132. Wan L, Dockendorff TC, Jongens TA, Dreyfuss G: Characterization of dFMR1, a Drosophila melanogaster homolog of the fragile X mental retardation protein. Mol Cell Biol 20:8536-8547 (2000).
133. Wang YH, Gellibolian R, Shimizu M, Wells RD, Griffith J: Long CCG triplet repeat blocks exclude nucleosomes: a possible mechanism for the nature of fragile sites in chromosomes. J molec Biol 263:511-516 (1996).
134. Warren ST, Sherman SL: The fragile X syndrome, in Scriver CR, Beaudet AL, Sly WS, Valle D (eds): The Metabolic and Molecular Basis of Inherited Disease, Vol 8, pp 1257-1289 (McGraw-Hill, New York 2001).
135. 15 forms a hairpin containing protonated cytosines and a distorted helix. Biochemistry 36: 3687-3699 (1997).
136. Zhang Y, O'Connor JP, Siomi MC, Srinivasan S, Dutra A, Nussbaum RL, Dreyfuss G: The fragile X mental retardation syndrome protein interacts with novel homologs FXR1 and FXR2. EMBO J 14:5358-5366 (1995).