A Family of Vertebrate-Specific Polycombs Encoded by the LCOR/LCORL Genes Balance PRC2 Subtype Activities
A Family of Vertebrate-Specific Polycombs Encoded by the LCOR/LCORL Genes Balance PRC2 Subtype Activities
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DOI：
10.1016/j.molcel.2018.03.005
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发表时间：
2018-05-03
期刊：
影响因子：
16
通讯作者：
Bracken, Adrian P.
中科院分区：
文献类型：
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作者：
Conway, Eric;Jerman, Emilia;Bracken, Adrian P.
多梳抑制复合物2（PRC 2）由核心亚基SUZ 1/2、EED、RBBP 4/7和EZH 1/2组成，负责组蛋白H3上赖氨酸27的单甲基化、二甲基化和三甲基化。虽然存在两种不同的形式，PRC2.1（含有一个多梳样蛋白）和PRC2.2（含有AEBP 2和JARID 2），但对它们的差异功能知之甚少。在这里，我们报告了一个脊椎动物特异性PRC2.1蛋白家族的发现，“PRC 2相关LCOR亚型1”（PALI 1）和PALI 2，分别由LCOR和LCORL基因位点编码。PALI 1在体外和体内促进PRC 2甲基转移酶活性，对小鼠发育至关重要。Pali 1和Aebp 2定义了相互排斥的拮抗PRC 2亚型，它们表现出不同的H3 K27三甲基化活性。这些PRC2.1/PRC2.2活性的平衡是在分化期间适当调节多梳靶基因所必需的。PALI 1/2可能将polycombs与转录辅助抑制因子联系起来，调节发育和癌症过程中的细胞特性。
The polycomb repressive complex 2 (PRC2) consists of core subunits SUZ12, EED, RBBP4/7, and EZH1/2 and is responsible for mono-, di-, and tri-methylation of lysine 27 on histone H3. Whereas two distinct forms exist, PRC2.1 (containing one polycomb-like protein) and PRC2.2 (containing AEBP2 and JARID2), little is known about their differential functions. Here, we report the discovery of a family of vertebrate-specific PRC2.1 proteins, "PRC2 associatedLCORisoform 1'' (PALI1) and PALI2, encoded by the LCOR and LCORL gene loci, respectively. PALI1 promotes PRC2 methyltransferase activity in vitro and in vivo and is essential for mouse development. Pali1 and Aebp2 define mutually exclusive, antagonistic PRC2 subtypes that exhibit divergent H3K27-tri-methylation activities. The balance of these PRC2.1/PRC2.2 activities is required for the appropriate regulation of polycomb target genes during differentiation. PALI1/2 potentially link polycombs with transcriptional co-repressors in the regulation of cellular identity during development and in cancer.