JARID1B is a histone H3 lysine 4 demethylase up-regulated in prostate cancer

被引：296

作者：

Xiang, Yang

Zhu, Ziqi

Han, Gang

Ye, Xiaolei

Xu, Bo

Peng, Zhouchun

Ma, Yuanjun

Yu, Yi

Lin, Hanqing

Chen, Adele Pin

Chen, Charlie Degui

机构：

[1] Chinese Acad Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China

[2] Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Syst Biol, Shanghai 200031, Peoples R China

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2007年 / 104卷 / 49期

基金：

中国国家自然科学基金;

关键词：

demethylation; methylation; transcription; JmjC domain;

D O I：

10.1073/pnas.0700735104

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：

Histone methylation is a dynamic process that participates in a diverse array of cellular processes and has been found to associate with cancer. Recently, several histone demethylases have been identified that catalyze the removal of methylation from histone H3 lysine residues. Through bioinformatic and biochemical analysis, we identified JARID1B as a H3K4 demethylase. Overexpression of JARID1B resulted in loss of tri-, di-, and monomethyl H3K4 but did not affect other histone lysine methylations. In vitro biochemical experiments demonstrated that JARID1B directly catalyzes the demethylation. The enzymatic activity requires the JmjC domain and uses Fe(II) and alpha-ketoglutarate as cofactors. Furthermore, we found that JARID1B is up-regulated in prostate cancer tissues, compared with benign prostate samples. We also demonstrated that JARID1B associates with androgen receptor and regulates its transcriptional activity. Thus, we identified JARID1B as a demethylase capable of removing three methyl groups from histone H3 lysine 4 and up-regulated in prostate cancer.

引用

页码：19226 / 19231

页数：6

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