PRC2.1 and PRC2.2 Synergize to Coordinate H3K27 Trimethylation

被引：129

作者：

Healy, Evan ^{[1
]}

Mucha, Marlena ^{[1
]}

Glancy, Eleanor ^{[1
]}

Fitzpatrick, Darren J. ^{[1
]}

Conway, Eric ^{[1
]}

Neikes, Hannah K. ^{[1
]}

Monger, Craig ^{[1
]}

Van Mierlo, Guido ^{[2
]}

Baltissen, Marijke P. ^{[2
]}

Koseki, Yoko ^{[3
]}

Vermeulen, Michiel ^{[2
]}

Koseki, Haruhiko ^{[3
]}

Bracken, Adrian P. ^{[1
]}

机构：

[1] Trinity Coll Dublin, Smurfit Inst Genet, Dublin 2, Ireland

[2] Radboud Univ Nijmegen, Radboud Inst Mol Life Sci, Fac Sci, Dept Mol Biol, Nijmegen, Netherlands

[3] RIKEN, Ctr Integrat Med Sci, IMS, Lab Dev Genet, Yokohama, Kanagawa, Japan

来源：

MOLECULAR CELL | 2019年 / 76卷 / 03期

基金：

爱尔兰科学基金会;

关键词：

HISTONE H3; CELL IDENTITY; POLYCOMB; COMPLEX; PRC1; EZH2; CHROMATIN; METHYLATION; PROTEIN; JARID2;

D O I：

10.1016/j.molcel.2019.08.012

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 repressive complex 2 (PRC2) is composed of EED, SUZ12, and EZH1/2 and mediates mono-, di-, and trimethylation of histone H3 at lysine 27. At least two independent subcomplexes exist, defined by their specific accessory proteins: PRC2.1 (PCL1-3, EPOP, and PALI1/2) and PRC2.2 (AEBP2 and JARID2). We show that PRC2.1 and PRC2.2 share the majority of target genes in mouse embryonic stem cells. The loss of PCL1-3 is sufficient to evict PRC2.1 from Polycomb target genes but only leads to a partial reduction of PRC2.2 and H3K27me3. Conversely, disruption of PRC2.2 function through the loss of either JARID2 or RING1A/B is insufficient to completely disrupt targeting of SUZ12 by PCLs. Instead, the combined loss of both PRC2.1 and PRC2.2 is required, leading to the global mislocalization of SUZ12. This supports a model in which the specific accessory proteins within PRC2.1 and PRC2.2 cooperate to direct H3K27me3 via both synergistic and independent mechanisms.

引用

页码：437 / +

页数：22

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