Rb targets histone H3 methylation and HP1 to promoters

被引：705

作者：

Nielsen, SJ

Schneider, R

Bauer, UM

Bannister, AJ

Morrison, A

O'Carroll, D

Firestein, R

Cleary, M

Jenuwein, T

Herrera, RE

Kouzarides, T

机构：

[1] Wellcome CRC Inst, Cambridge CB2 1QR, England

[2] Dept Pathol, Cambridge CB2 1QR, England

[3] Baylor Coll Med, Dept Mol & Cellular Biol, Breast Ctr, Houston, TX 77030 USA

[4] Vienna Bioctr, Res Inst Mol Pathol, A-1030 Vienna, Austria

[5] Stanford Univ, Med Ctr, Dept Pathol, Stanford, CA 94305 USA

来源：

NATURE | 2001年 / 412卷 / 6846期

关键词：

D O I：

10.1038/35087620

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

In eukaryotic cells the histone methylase SUV39H1 and the methyl-lysine binding protein HP1 functionally interact to repress transcription at heterochromatic sites(1). Lysine 9 of histone H3 is methylated by SUV39H1 (ref. 2), creating a binding site for the chromo domain of HP1 (refs 3, 4). Here we show that SUV39H1 and HP1 are both involved in the repressive functions of the retinoblastoma (Rb) protein. Rb associates with SUV39H1 and HP1 in vivo by means of its pocket domain. SUV39H1 cooperates with Rb to repress the cyclin E promoter, and in fibroblasts that are disrupted for SUV39, the activity of the cyclin E and cyclin A2 genes are specifically elevated. Chromatin immunoprecipitations show that Rb is necessary to direct methylation of histone H3, and is necessary for binding of HP1 to the cyclin E promoter. These results indicate that the SUV39H1-HP1 complex is not only involved in heterochromatic silencing but also has a role in repression of euchromatic genes by Rb and perhaps other co-repressor proteins.

引用

页码：561 / 565

页数：5

共 22 条

[1] Functional mammalian homologues of the Drosophila PEV-modifier Su(var)3-9 encode centromere-associated proteins which complex with the heterochromatin component M31 [J].