The histone H2B-specific ubiquitin ligase RNF20/hBRE1 acts as a putative tumor suppressor through selective regulation of gene expression

被引：227

作者：

Shema, Efrat ^{[1
]}

Tirosh, Itay ^{[2
]}

Aylon, Yael ^{[1
]}

Huang, Jing ^{[3
]}

Ye, Chaoyang ^{[3
]}

Moskovits, Neta ^{[1
]}

Raver-Shapira, Nina ^{[1
]}

Minsky, Neri ^{[1
]}

Pirngruber, Judith ^{[4
]}

Tarcic, Gabi ^{[5
]}

Hublarova, Pavla ^{[6
]}

Moyal, Lilach ^{[7
]}

Gana-Weisz, Mali ^{[7
]}

Shiloh, Yosef ^{[7
]}

Yarden, Yossef ^{[5
]}

Johnsen, Steven A. ^{[4
]}

Vojtesek, Borivoj ^{[6
]}

Berger, Shelley L. ^{[3
]}

Oren, Moshe ^{[1
]}

机构：

[1] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel

[2] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel

[3] Wistar Inst Anat & Biol, Gene Express & Regulat Program, Philadelphia, PA 19104 USA

[4] Gottingen Ctr Mol Biosci, Dept Mol Oncol, D-37077 Gottingen, Germany

[5] Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel

[6] Masaryk Mem Canc Inst, Dept Oncol & Expt Pathol, Brno 65653, Czech Republic

[7] Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel

来源：

GENES & DEVELOPMENT | 2008年 / 22卷 / 19期

关键词：

RNF20; BRE1; H2B ubiquitylation; tumor suppressor; transcription;

D O I：

10.1101/gad.1703008

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Histone monoubiquitylation is implicated in critical regulatory processes. We explored the roles of histone H2B ubiquitylation in human cells by reducing the expression of hBRE1/RNF20, the major H2B-specific E3 ubiquitin ligase. While H2B ubiquitylation is broadly associated with transcribed genes, only a subset of genes was transcriptionally affected by RNF20 depletion and abrogation of H2B ubiquitylation. Gene expression dependent on RNF20 includes histones H2A and H2B and the p53 tumor suppressor. In contrast, RNF20 suppresses the expression of several proto-oncogenes, which reside preferentially in closed chromatin and are modestly transcribed despite bearing marks usually associated with high transcription rates. Remarkably, RNF20 depletion augmented the transcriptional effects of epidermal growth factor (EGF), increased cell migration, and elicited transformation and tumorigenesis. Furthermore, frequent RNF20 promoter hypermethylation was observed in tumors. RNF20 may thus be a putative tumor suppressor, acting through selective regulation of a distinct subset of genes.

引用

页码：2664 / 2676

页数：13

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