ATR-X Syndrome Protein Targets Tandem Repeats and Influences Allele-Specific Expression in a Size-Dependent Manner

被引：335

作者：

Law, Martin J. ^{[1
]}

Lower, Karen M. ^{[1
]}

Voon, Hsiao P. J. ^{[1
]}

Hughes, Jim R. ^{[1
]}

Garrick, David ^{[1
]}

Viprakasit, Vip ^{[3
]}

Mitson, Matthew ^{[1
]}

De Gobbi, Marco ^{[1
]}

Marra, Marco ^{[7
]}

Morris, Andrew ^{[4
]}

Abbott, Aaron ^{[4
]}

Wilder, Steven P. ^{[5
]}

Taylor, Stephen ^{[2
]}

Santos, Guilherme M. ^{[6
]}

Cross, Joe ^{[1
]}

Ayyub, Helena ^{[1
]}

Jones, Steven ^{[7
]}

Ragoussis, Jiannis ^{[4
]}

Rhodes, Daniela ^{[6
]}

Dunham, Ian ^{[5
]}

Higgs, Douglas R. ^{[1
]}

Gibbons, Richard J. ^{[1
]}

机构：

[1] John Radcliffe Hosp, Weatherall Inst Mol Med, MRC, Mol Haematol Unit, Oxford OX3 9DS, England

[2] John Radcliffe Hosp, Weatherall Inst Mol Med, Computat Biol Res Grp, Oxford OX3 9DS, England

[3] Mahidol Univ, Siriaj Hosp, Fac Med, Dept Paediat, Bangkok 10700, Thailand

[4] Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England

[5] European Bioinformat Inst, Cambridge CB10 1SD, England

[6] MRC, Struct Studies Div, Mol Biol Lab, Cambridge CB2 0QH, England

[7] Univ British Columbia, BCCA Genome Sci Ctr, Vancouver, BC V6T 1Z4, Canada

来源：

CELL | 2010年 / 143卷 / 03期

基金：

英国医学研究理事会;

关键词：

LINKED MENTAL-RETARDATION; CHROMATIN IMMUNOPRECIPITATION; HISTONE CHAPERONE; MUTATIONS; LOCALIZATION; DAXX; HETEROCHROMATIN; QUADRUPLEXES; BINDING; GENES;

D O I：

10.1016/j.cell.2010.09.023

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

ATRX is an X-linked gene of the SWI/SNF family, mutations in which cause syndromal mental retardation and downregulation of a-globin expression. Here we show that ATRX binds to tandem repeat (TR) sequences in both telomeres and euchromatin. Genes associated with these TRs can be dysregulated when ATRX is mutated, and the change in expression is determined by the size of the TR, producing skewed allelic expression. This reveals the characteristics of the affected genes, explains the variable phenotypes seen with identical ATRX mutations, and illustrates a new mechanism underlying variable penetrance. Many of the TRs are G rich and predicted to form non-B DNA structures (including G-quadruplex) in vivo. We show that ATRX binds G-quadruplex structures in vitro, suggesting a mechanism by which ATRX may play a role in various nuclear processes and how this is perturbed when ATRX is mutated.

引用

页码：367 / 378

页数：12

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