JMJD3 is a histone H3K27 demethylase

被引：227

作者：

Xiang, Yang ^{[1
]}

Zhu, Ziqi ^{[1
]}

Han, Gang ^{[1
]}

Lin, Hanqing ^{[1
]}

Xu, Longyong ^{[1
]}

Chen, Charlie Degui ^{[1
]}

机构：

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

来源：

CELL RESEARCH | 2007年 / 17卷 / 10期

关键词：

histone methylation; demethylase; JMJD3; H3K27; prostate cancer;

D O I：

10.1038/cr.2007.83

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Histone methylation is an important epigenetic phenomenon that participates in a diverse array of cellular processes and has been found to be associated with cancer. Recent identification of several histone demethylases has proved that histone methylation is a reversible process. Through a candidate approach, we have biochemically identified JMJD3 as an H3K27 demethylase. Transfection of JMJD3 into HeLa cells caused a specific reduction of trimethyl H3K27, but had no effect on di- and monomethyl H3K27, or histone lysine methylations on H3K4 and H3K9. The enzymatic activity requires the JmjC domain and the conserved histidine that has been suggested to be important for a cofactor binding. In vitro biochemical experiments demonstrated that JMJD3 directly catalyzes the demethylation. In addition, we found that JMJD3 is upregulated in prostate cancer, and its expression is higher in metastatic prostate cancer. Thus, we identified JMJD3 as a demethylase capable of removing the trimethyl group from histone H3 lysine 27 and upregulated in prostate cancer.

引用

页码：850 / 857

页数：8

共 29 条

[1]

AGGER K, 2007, NATURE, DOI DOI 10.1038/NATURE06147

[2] Reversing histone methylation [J].

Bannister, AJ ;

Kouzarides, T .

NATURE, 2005, 436 (7054) :1103-1106

[3] Arginine methylation: An emerging regulator of protein function [J].

Bedford, MT ;

Richard, S .

MOLECULAR CELL, 2005, 18 (03) :263-272

[4] Molecular determinants of resistance to antiandrogen therapy [J].

Chen, CD ;

Welsbie, DS ;

Tran, C ;

Baek, SH ;

Chen, R ;

Vessella, R ;

Rosenfeld, MG ;

Sawyers, CL .

NATURE MEDICINE, 2004, 10 (01) :33-39

[5] Structural insights into histone demethylation by JMJD2 family members [J].

Chen, Zhongzhou ;

Zang, Jianye ;

Whetstine, Johnathan ;

Hong, Xia ;

Davrazou, Foteini ;

Kutateladze, Tatiana G. ;

Simpson, Michael ;

Mao, Qilong ;

Pan, Cheol-Ho ;

Dai, Shaodong ;

Hagman, James ;

Hansen, Kirk ;

Shi, Yang ;

Zhang, Gongyi .

CELL, 2006, 125 (04) :691-702

[6] RBP2 belongs to a family of demethylases, specific for tri- and dimethylated lysine 4 on histone 3 [J].

Christensen, Jesper ;

Agger, Karl ;

Cloos, Paul A. C. ;

Pasini, Diego ;

Rose, Simon ;

Sennels, Lau ;

Rappsilber, Juri ;

Hansen, Klaus H. ;

Salcini, Anna Elisabetta ;

Helin, Kristian .

CELL, 2007, 128 (06) :1063-1076

[7] The putative oncogene GASC1 demethylates tri- and dimethylated lysine 9 on histone H3 [J].

Cloos, Paul A. C. ;

Christensen, Jesper ;

Agger, Karl ;

Maiolica, Alessio ;

Rappsilber, Juri ;

Antal, Torben ;

Hansen, Klaus H. ;

Helin, Kristian .

NATURE, 2006, 442 (7100) :307-311

[8] The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases [J].

Iwase, Shigeki ;

Lan, Fei ;

Bayliss, Peter ;

de la Torre-Ubieta, Luis ;

Huarte, Maite ;

Qi, Hank H. ;

Whetstine, Johnathan R. ;

Bonni, Azad ;

Roberts, Thomas M. ;

Shi, Yang .

CELL, 2007, 128 (06) :1077-1088

[9] The retinoblastoma binding protein RBP2 is an H3K4 demethylase [J].

Klose, Robert J. ;

Yan, Qin ;

Tothova, Zuzana ;

Yamane, Kenichi ;

Erdjument-Bromage, Hediye ;

Tempst, Paul ;

Gilliland, D. Gary ;

Zhang, Yi ;

Kaelin, William G., Jr. .

CELL, 2007, 128 (05) :889-900

[10] JmjC-domain-containing proteins and histone demethylation [J].

Klose, Robert J. ;

Kallin, Eric M. ;

Zhang, Yi .

NATURE REVIEWS GENETICS, 2006, 7 (09) :715-727

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