Additional sex combs-like 2 is required for polycomb repressive complex 2 binding at select targets.
Additional sex combs-like 2 is required for polycomb repressive complex 2 binding at select targets.
复制标题
多梳抑制复合物 2 在选定靶点上的结合需要额外的性梳状 2。
DOI：
10.1371/journal.pone.0073983
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wang QT
中科院分区：
文献类型：
--
作者：
Lai HL;Wang QT
Polycomb Group（PcG）蛋白是基因表达的表观遗传阻遏物。果蝇额外性梳（Asx）基因及其哺乳动物同源物在遗传分析中表现出PcG功能，然而，Asx家族蛋白介导基因阻遏的机制还不清楚。ASXL2是Asx的三种哺乳动物同源物之一，在哺乳动物心脏中高度表达，并且是维持心脏功能所必需的。我们先前已经表明，Asxl2缺陷导致组蛋白H3赖氨酸27三甲基化（H3K27me3）的整体水平降低，H3K27me3是由Polycomb抑制复合物2（PRC2）产生的抑制标记。在这里，我们确定了心脏中的几个ASXL2靶基因，并研究了ASXL2促进其抑制的机制。我们发现，Asxl2缺陷的心脏是有缺陷的H3K27me2转换为H3K27me3和去除泛素从单泛素化组蛋白H2A。ASXL2和PRC2在成人心脏中相互作用并共定位于靶启动子。ASXL2对于PRC2的结合和H3K27me3在靶启动子处的富集是必需的。这些结果增加了一个新的视角，我们了解的机制，调节PcG活动和基因阻遏。
Polycomb Group (PcG) proteins are epigenetic repressors of gene expression. The Drosophila Additional sex combs (Asx) gene and its mammalian homologs exhibit PcG function in genetic assays; however, the mechanism by which Asx family proteins mediate gene repression is not well understood. ASXL2, one of three mammalian homologs for Asx, is highly expressed in the mammalian heart and is required for the maintenance of cardiac function. We have previously shown that Asxl2 deficiency results in a reduction in the bulk level of histone H3 lysine 27 trimethylation (H3K27me3), a repressive mark generated by the Polycomb Repressive Complex 2 (PRC2). Here we identify several ASXL2 target genes in the heart and investigate the mechanism by which ASXL2 facilitates their repression. We show that the Asxl2-deficient heart is defective in converting H3K27me2 to H3K27me3 and in removing ubiquitin from mono-ubiquitinated histone H2A. ASXL2 and PRC2 interact in the adult heart and co-localize to target promoters. ASXL2 is required for the binding of PRC2 and for the enrichment of H3K27me3 at target promoters. These results add a new perspective to our understanding of the mechanisms that regulate PcG activity and gene repression.
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DOI：
10.2741/3898
发表时间：
2011-06-01
期刊：
Frontiers in bioscience (Landmark edition)
影响因子：
--
作者：
Huang ZM;Gold JI;Koch WJ
通讯作者：
Koch WJ
影响因子：
50.3
作者：
Abdel-Wahab O;Adli M;LaFave LM;Gao J;Hricik T;Shih AH;Pandey S;Patel JP;Chung YR;Koche R;Perna F;Zhao X;Taylor JE;Park CY;Carroll M;Melnick A;Nimer SD;Jaffe JD;Aifantis I;Bernstein BE;Levine RL
通讯作者：
Levine RL
影响因子：
4
作者：
Gould, A
通讯作者：
Gould, A
影响因子：
16
作者：
Cao, R;Zhang, Y
通讯作者：
Zhang, Y
影响因子：
3.7
作者：
Baskind HA;Na L;Ma Q;Patel MP;Geenen DL;Wang QT
通讯作者：
Wang QT