Phf19 links methylated Lys36 of histone H3 to regulation of Polycomb activity

被引：183

作者：

Ballare, Cecilia ^{[1
,2
]}

Lange, Martin ^{[1
,2
]}

Lapinaite, Audrone ^{[3
]}

Martin, Gloria Mas ^{[4
]}

Morey, Lluis ^{[1
,2
]}

Pascual, Gloria ^{[1
,2
]}

Liefke, Robert ^{[5
,6
,7
]}

Simon, Bernd ^{[3
]}

Shi, Yang ^{[5
,6
,7
]}

Gozani, Or ^{[4
]}

Carlomagno, Teresa ^{[3
]}

Aznar Benitah, Salvador ^{[1
,2
,8
]}

Di Croce, Luciano ^{[1
,2
,8
]}

机构：

[1] Ctr Genom Regulat, Dept Gene Regulat & Stem Cells, Barcelona, Spain

[2] Univ Pompeu Fabra, Barcelona, Spain

[3] European Mol Biol Lab, Struct & Computat Biol Unit, Heidelberg, Germany

[4] Stanford Univ, Dept Biol Sci, Stanford, CA 94305 USA

[5] Harvard Univ, Childrens Hosp, Sch Med, Div Newborn Med,Dept Med, Boston, MA 02115 USA

[6] Harvard Univ, Childrens Hosp, Sch Med, Program Epigenet,Dept Med, Boston, MA 02115 USA

[7] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA

[8] ICREA, Barcelona, Spain

来源：

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

基金：

美国国家卫生研究院;

关键词：

EMBRYONIC STEM-CELLS; NMR STRUCTURE CALCULATION; MOLECULAR-BASIS; GROUP PROTEINS; TARGET GENES; DEVELOPMENTAL REGULATORS; MOUSE DEVELOPMENT; HIGH-SENSITIVITY; CHEMICAL-SHIFT; SELF-RENEWAL;

D O I：

10.1038/nsmb.2434

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 transcriptional repressors with essential roles in embryonic development. Polycomb repressive complex 2 (PRC2) contains the methyltransferase activity for Lys27. However, the role of other histone modifications in regulating PRC2 activity is just beginning to be understood. Here we show that direct recognition of methylated histone H3 Lys36 (H3K36me), a mark associated with activation, by the PRC2 subunit Phf19 is required for the full enzymatic activity of the PRC2 complex. Using NMR spectroscopy, we provide structural evidence for this interaction. Furthermore, we show that Phf19 binds to a subset of PRC2 targets in mouse embryonic stem cells and that this is required for their repression and for H3K27me3 deposition. These findings show that the interaction of Phf19 with H3K36me2 and H3K36me3 is essential for PRC2 complex activity and for proper regulation of gene repression in embryonic stem cells.

引用

页码：1257 / +

页数：11

共 71 条

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