Polycomb PHF19 binds H3K36me3 and recruits PRC2 and demethylase NO66 to embryonic stem cell genes during differentiation

被引：192

作者：

Brien, Gerard L. ^{[1
]}

Gambero, Guillermo ^{[2
]}

O'Connell, David J. ^{[2
]}

Jerman, Emilia ^{[1
]}

Turner, Siobhan A. ^{[1
]}

Egan, Chris M. ^{[1
]}

Dunne, Eiseart J. ^{[1
]}

Jurgens, Maike C. ^{[2
]}

Wynne, Kieran ^{[2
]}

Piao, Lianhua ^{[3
]}

Lohan, Amanda J. ^{[2
]}

Ferguson, Neil ^{[2
]}

Shi, Xiaobing ^{[3
]}

Sinha, Krishna M. ^{[4
]}

Loftus, Brendan J. ^{[2
]}

Cagney, Gerard ^{[2
]}

Bracken, Adrian P. ^{[1
,5
]}

机构：

[1] Trinity Coll Dublin, Smurfit Inst Genet, Dublin, Ireland

[2] Univ Coll Dublin, Conway Inst, Dublin, Ireland

[3] Univ Texas MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA

[5] Natl Childrens Hosp, Adelaide & Meath Hosp, Dublin, Ireland

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2012年 / 19卷 / 12期

基金：

爱尔兰科学基金会;

关键词：

HISTONE METHYLTRANSFERASE ACTIVITY; H3; LYSINE-27; METHYLATION; GROUP PROTEINS; TARGET GENES; H2A UBIQUITYLATION; ZESTE PROTEIN; COMPLEX; EZH2; TRIMETHYLATION; CANCER;

D O I：

10.1038/nsmb.2449

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：

Polycomb group proteins are repressive chromatin modifiers with essential roles in metazoan development, cellular differentiation and cell fate maintenance. How Polycomb proteins access active chromatin to confer transcriptional silencing during lineage transitions remains unclear. Here we show that the Polycomb repressive complex 2 (PRC2) component PHF19 binds trimethylated histone H3 Lys36 (H3K36me3), a mark of active chromatin, via its Tudor domain. PHF19 associates with the H3K36me3 demethylase NO66, and it is required to recruit the PRC2 complex and NO66 to stem cell genes during differentiation, leading to PRC2-mediated trimethylation of histone H3 Lys27 (H3K27), loss of H3K36me3 and transcriptional silencing. We propose a model whereby PHF19 functions during mouse embryonic stem cell differentiation to transiently bind the H3K36me3 mark via its Tudor domain, forming essential contact points that allow recruitment of PRC2 and H3K36me3 demethylase activity to active gene loci during their transition to a Polycomb-repressed state.

引用

页码：1273 / +

页数：11

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