L3MBTL2 protein acts in concert with PcG protein-mediated monoubiquitination of H2A to establish a repressive chromatin structure.
L3MBTL2 protein acts in concert with PcG protein-mediated monoubiquitination of H2A to establish a repressive chromatin structure.
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DOI：
10.1016/j.molcel.2011.04.004
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发表时间：
2011-05-20
期刊：
影响因子：
16
通讯作者：
Reinberg D
中科院分区：
文献类型：
--
作者：
Trojer P;Cao AR;Gao Z;Li Y;Zhang J;Xu X;Li G;Losson R;Erdjument-Bromage H;Tempst P;Farnham PJ;Reinberg D
鉴于PcG蛋白RING1、RING2和PCGF6/MBLR的共同存在，我们已经鉴定出人类含MBT结构域的蛋白L3MBTL2是一个蛋白质复合物的组成部分，我们将其称为Polycomb repression complex 1 (PRC1)-样4 （PRC1L4）。PRC1L4还含有已知在转录抑制中起作用的E2F6和CBX3/ HPlγ。prcil4介导的抑制需要L3MBTL2以不依赖组蛋白修饰的方式压实染色质。全基因组定位分析发现，数百个基因同时与L3MBTL2和E2F6结合，优先围绕转录起始位点，与其他E2Fs或L3MBTL1（另一种与RB1相互作用的mbt结构域蛋白）的靶向位点几乎没有重叠。l3mbtl2特异性RNAi导致靶基因表达增加，显示H2A赖氨酸119单泛素化显著降低。这些发现突出了PcG/MBT合作，在不需要组蛋白赖氨酸甲基化标记的情况下获得抑制染色质。
We have identified human MBT domain-containing protein L3MBTL2 as an integral component of a protein complex that we termed Polycomb Repressive Complex 1 (PRC1)-like 4 (PRC1L4) given the co-presence of PcG proteins RING1, RING2 and PCGF6/MBLR. PRC1L4 also contained E2F6 and CBX3/ HPlγ known to function in transcriptional repression. PRCIL4-mediated repression necessitated L3MBTL2 that compacted chromatin in a histone modification-independent manner. Genome-wide location analyses identified several hundred genes simultaneously bound by L3MBTL2 and E2F6, preferentially around transcriptional start sites that exhibited little overlap with those targeted by other E2Fs or by L3MBTL1, another MBT-domain containing protein that interacts with RB1. L3MBTL2-specific RNAi resulted in increased expression of target genes that exhibited a significant reduction in H2A lysine 119 monoubiquitination. These findings highlight a PcG/MBT collaboration that attains repressive chromatin without entailing histone lysine methylation marks.
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