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KDM2B将多梳抑制复合物1(PRC1)与CpG岛的识别联系起来。

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

作者信息

Farcas Anca M, Blackledge Neil P, Sudbery Ian, Long Hannah K, McGouran Joanna F, Rose Nathan R, Lee Sheena, Sims David, Cerase Andrea, Sheahan Thomas W, Koseki Haruhiko, Brockdorff Neil, Ponting Chris P, Kessler Benedikt M, Klose Robert J

机构信息

Department of Biochemistry , University of Oxford , Oxford , UK.

出版信息

Elife. 2012 Dec 18;1:e00205. doi: 10.7554/eLife.00205.

Abstract

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.DOI:http://dx.doi.org/10.7554/eLife.00205.001.

摘要

CpG岛(CGIs)与大多数哺乳动物基因启动子相关联。一部分CGIs充当多梳反应元件(PREs),并被多梳沉默系统识别,以调控参与早期发育的基因的表达。CGIs作为多梳抑制复合物的成核位点在机制上是如何发挥作用的仍不清楚。在此,我们发现KDM2B(FBXL10)特异性识别CGIs中的非甲基化DNA,并募集多梳抑制复合物1(PRC1)。这有助于组蛋白H2A赖氨酸119泛素化(H2AK119ub1)和基因抑制。出乎意料的是,我们还发现CGIs在整个基因组中都被低水平的PRC1占据,这表明KDM2B-PRC1复合物可能对与CGIs相关的基因进行筛选,以确定其对多梳介导的沉默的敏感性。这些观察结果证明了KDM2B对CGIs的识别与多梳抑制系统的靶向之间存在意想不到的直接联系。这为描述CGIs作为哺乳动物PREs的功能的新模型提供了基础。DOI:http://dx.doi.org/10.7554/eLife.00205.001

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3f2/3524939/83de5f2890ae/elife00205f001.jpg

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