Molecular Interplay of the Noncoding RNA ANRIL and Methylated Histone H3 Lysine 27 by Polycomb CBX7 in Transcriptional Silencing of INK4a

被引：1215

作者：

Yap, Kyoko L. ^{[1
]}

Li, Side ^{[2
]}

Munoz-Cabello, Ana M. ^{[3
]}

Raguz, Selina ^{[3
]}

Zeng, Lei ^{[1
]}

Mujtaba, Shiraz ^{[1
]}

Gil, Jesus ^{[3
]}

Walsh, Martin J. ^{[1
,2
]}

Zhou, Ming-Ming ^{[1
]}

机构：

[1] Mt Sinai Sch Med, Dept Struct & Chem Biol, New York, NY 10029 USA

[2] Mt Sinai Sch Med, Dept Pediat, New York, NY 10029 USA

[3] Univ London Imperial Coll Sci Technol & Med, Ctr Clin Sci, MRC, Cell Proliferat Grp, London W12 0NN, England

来源：

MOLECULAR CELL | 2010年 / 38卷 / 05期

基金：

英国医学研究理事会; 美国国家科学基金会; 美国国家卫生研究院;

关键词：

CORONARY-ARTERY-DISEASE; GROUP PROTEINS; X-CHROMOSOME; LOCUS; CHROMATIN; CELLS; CHROMODOMAIN; DEMETHYLASE; REPRESSION; EXPRESSION;

D O I：

10.1016/j.molcel.2010.03.021

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：

Expression of the INK4b/ARF/INK4a tumor suppressor locus in normal and cancerous cell growth is controlled by methylation of histone H3 at lysine 27 (H3K27me) as directed by the Polycomb group proteins. The antisense noncoding RNA ANRIL of the INK4b/ARF/INK4a locus is also important for expression of the protein-coding genes in cis, but its mechanism has remained elusive. Here we report that chromobox 7 (CBX7) within the polycomb repressive complex 1 binds to ANRIL, and both CBX7 and ANRIL are found at elevated levels in prostate cancer tissues. In concert with H3K27me recognition, binding to RNA contributes to CBX7 function, and disruption of either interaction impacts the ability of CBX7 to repress the INK4b/ARF/INK4a locus and control senescence. Structure-guided analysis reveals the molecular interplay between noncoding RNA and H3K27me as mediated by the conserved chromodomain. Our study suggests a mechanism by which noncoding RNA participates directly in epigenetic transcriptional repression.

引用

页码：662 / 674

页数：13

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