Epigenetic changes and non-coding expanded repeats

被引：28

作者：

Nakamori, Masayuki ^{[1
]}

Thornton, Charles ^{[1
]}

机构：

[1] Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA

来源：

NEUROBIOLOGY OF DISEASE | 2010年 / 39卷 / 01期

关键词：

Myotonic dystrophy; RNA dominance; Epigenetics; Friedreich ataxia; Fragile X syndrome; MBNL; Trinucleotide repeat; FRAGILE-X-SYNDROME; MYOTONIC-DYSTROPHY TYPE-1; TRINUCLEOTIDE REPEAT; FRIEDREICH ATAXIA; TREMOR/ATAXIA SYNDROME; MESSENGER-RNA; MUSCLEBLIND PROTEINS; BINDING PROTEIN; NUCLEAR FOCI; CTG REPEATS;

D O I：

10.1016/j.nbd.2010.02.004

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Many neurogenetic disorders are caused by unstable expansions of tandem repeats. Some of the causal mutations are located in non-protein-coding regions of genes. When pathologically expanded, these repeats can trigger focal epigenetic changes that repress the expression of the mutant allele. When the mutant gene is not repressed, the transcripts containing the expanded repeat can give rise to a toxic gain-of-function by the mutant RNA. These two mechanisms, heterochromatin-mediated gene repression and RNA dominance, produce a wide range of neurodevelopmental and neurodegenerative abnormalities. Here we review the mechanisms of gene dysregulation induced by non-coding repeat expansions, and early indications that some of these disorders may prove to be responsive to therapeutic intervention. (C) 2010 Elsevier Inc. All rights reserved.

引用

页码：21 / 27

页数：7

共 113 条

[1] The Friedreich ataxia GAA repeat expansion mutation induces comparable epigenetic changes in human and transgenic mouse brain and heart tissues [J].

Al-Mahdawi, Sahar ;

Pinto, Ricardo Mouro ;

Ismail, Ozama ;

Varshney, Dhaval ;

Lymperi, Stefania ;

Sandi, Chiranjeevi ;

Trabzuni, Daniah ;

Pook, Mark .

HUMAN MOLECULAR GENETICS, 2008, 17 (05) :735-746

[2] Cis and trans effects of the myotonic dystrophy (DM) mutation in a cell culture model [J].

Amack, JD ;

Paguio, AP ;

Mahadevan, MS .

HUMAN MOLECULAR GENETICS, 1999, 8 (11) :1975-1984

[3] The pathogenic mechanisms of polyglutamine diseases and current therapeutic strategies [J].

Bauer, Peter O. ;

Nukina, Nobuyuki .

JOURNAL OF NEUROCHEMISTRY, 2009, 110 (06) :1737-1765

[4] The mGIuR theory of fragile X mental retardation [J].

Bear, MF ;

Huber, KM ;

Warren, ST .

TRENDS IN NEUROSCIENCES, 2004, 27 (07) :370-377

[5] The GAA triplet-repeat expansion in Friedreich ataxia interferes with transcription and may be associated with an unusual DNA structure [J].

Bidichandani, SI ;

Ashizawa, T ;

Patel, PI .

AMERICAN JOURNAL OF HUMAN GENETICS, 1998, 62 (01) :111-121

[6] MOLECULAR-BASIS OF MYOTONIC-DYSTROPHY - EXPANSION OF A TRINUCLEOTIDE (CTG) REPEAT AT THE 3' END OF A TRANSCRIPT ENCODING A PROTEIN-KINASE FAMILY MEMBER [J].

BROOK, JD ;

MCCURRACH, ME ;

HARLEY, HG ;

BUCKLER, AJ ;

CHURCH, D ;

ABURATANI, H ;

HUNTER, K ;

STANTON, VP ;

THIRION, JP ;

HUDSON, T ;

SOHN, R ;

ZEMELMAN, B ;

SNELL, RG ;

RUNDLE, SA ;

CROW, S ;

DAVIES, J ;

SHELBOURNE, P ;

BUXTON, J ;

JONES, C ;

JUVONEN, V ;

JOHNSON, K ;

HARPER, PS ;

SHAW, DJ ;

HOUSMAN, DE .

CELL, 1992, 68 (04) :799-808

[7] Friedreich's ataxia: Autosomal recessive disease caused by an intronic GAA triplet repeat expansion [J].

Campuzano, V ;

Montermini, L ;

Molto, MD ;

Pianese, L ;

Cossee, M ;

Cavalcanti, F ;

Monros, E ;

Rodius, F ;

Duclos, F ;

Monticelli, A ;

Zara, F ;

Canizares, J ;

Koutnikova, H ;

Bidichandani, SI ;

Gellera, C ;

Brice, A ;

Trouillas, P ;

DeMichele, G ;

Filla, A ;

DeFrutos, R ;

Palau, F ;

Patel, PI ;

DiDonato, S ;

Mandel, JL ;

Cocozza, S ;

Koenig, M ;

Pandolfo, M .

SCIENCE, 1996, 271 (5254) :1423-1427

[8] Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes [J].

Campuzano, V ;

Montermini, L ;

Lutz, Y ;

Cova, L ;

Hindelang, C ;

Jiralerspong, S ;

Trottier, Y ;

Kish, SJ ;

Faucheux, B ;

Trouillas, P ;

Authier, FJ ;

Durr, A ;

Mandel, JL ;

Vescovi, A ;

Pandolfo, M ;

Koenig, M .

HUMAN MOLECULAR GENETICS, 1997, 6 (11) :1771-1780

[9] Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing [J].

Charlet-B, N ;

Savkur, RS ;

Singh, G ;

Philips, AV ;

Grice, EA ;

Cooper, TA .

MOLECULAR CELL, 2002, 10 (01) :45-53

[10] Antisense transcription and heterochromatin at the DM1 CTG repeats are constrained by CTCF [J].

Cho, DH ;

Thienes, CP ;

Mahoney, SE ;

Analau, E ;

Filippova, GN ;

Tapscott, SJ .

MOLECULAR CELL, 2005, 20 (03) :483-489

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