KDM2B links the Polycomb Repressive Complex 1 (PRC1) to recognition of CpG islands

被引：346

作者：

Farcas, Anca M. ^{[1
]}

Blackledge, Neil P. ^{[1
]}

Sudbery, Ian ^{[2
]}

Long, Hannah K. ^{[1
,3
]}

McGouran, Joanna F. ^{[4
]}

Rose, Nathan R. ^{[1
]}

Lee, Sheena ^{[5
]}

Sims, David ^{[2
]}

Cerase, Andrea ^{[1
]}

Sheahan, Thomas W. ^{[1
]}

Koseki, Haruhiko ^{[6
]}

Brockdorff, Neil ^{[1
]}

Ponting, Chris P. ^{[2
]}

Kessler, Benedikt M. ^{[4
]}

Klose, Robert J. ^{[1
]}

机构：

[1] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England

[2] Univ Oxford, Dept Physiol Anat & Genet, MRC Funct Genom Unit, CGAT, Oxford, England

[3] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Mol Haematol Unit, Oxford OX3 9DU, England

[4] Univ Oxford, Nuffield Dept Clin Med, Ctr Cellular & Mol Physiol, Cent Prote Facil,Ubiquitin Proteolysis Grp, Oxford, England

[5] Univ Oxford, Dept Physiol Anat & Genet, Oxford, England

[6] RIKEN Res Ctr Allergy & Immunol, Lab Dev Genet, Yokohama, Kanagawa, Japan

来源：

ELIFE | 2012年 / 1卷

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

EMBRYONIC STEM-CELLS; HISTONE METHYLTRANSFERASE ACTIVITY; GROUP PROTEINS RING1A/B; BINDING-PROTEIN; CHROMATIN-STRUCTURE; X-INACTIVATION; TRANSCRIPTIONAL REPRESSOR; DEVELOPMENTAL REGULATORS; H2A UBIQUITYLATION; EPIGENETIC MEMORY;

D O I：

10.7554/eLife.00205

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

CpG islands (CGIs) are associated with most mammalian gene promoters. A subset of CGIs act as polycomb response elements (PREs) and are recognized by the polycomb silencing systems to regulate expression of genes involved in early development. How CGIs function mechanistically as nucleation sites for polycomb repressive complexes remains unknown. Here we discover that KDM2B (FBXL10) specifically recognizes non-methylated DNA in CGIs and recruits the polycomb repressive complex 1 (PRC1). This contributes to histone H2A lysine 119 ubiquitylation (H2AK119ub1) and gene repression. Unexpectedly, we also find that CGIs are occupied by low levels of PRC1 throughout the genome, suggesting that the KDM2B-PRC1 complex may sample CGI-associated genes for susceptibility to polycomb-mediated silencing. These observations demonstrate an unexpected and direct link between recognition of CGIs by KDM2B and targeting of the polycomb repressive system. This provides the basis for a new model describing the functionality of CGIs as mammalian PREs.

引用

页数：26

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