Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein
Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein
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DOI：
10.1101/gad.1035902
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发表时间：
2002-11-15
影响因子：
10.5
通讯作者：
Reinberg, D
中科院分区：
文献类型：
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作者：
Kuzmichev, A;Nishioka, K;Reinberg, D
Zust的增强子[E(Z)]是一种多梳基转录抑制因子，是SET结构域蛋白家族的创始成员之一。一些SET结构域蛋白具有固有的组蛋白甲基转移酶(HMT)活性。然而，重组E(Z)蛋白在HMT检测中被发现是无效的。在这里，我们报告了一个多蛋白E(Z)复合体的分离，该复合体包含额外的性梳子、Zust-12[SU(Z)12]的抑制子和组蛋白结合蛋白RbAp46/RbAp48。我们称之为多梳抑制复合体(PRC)2，它对组蛋白H3的Lys 9(K9)和Lys 27(K27)具有特异性的HMT活性。PRC2的HMT活性依赖于E(Z)蛋白中完整的SET结构域。我们假设E(Z)蛋白的转录抑制涉及依赖甲基化的PRC1的招募。位置效应差异的强抑制因子SU(Z)12在PRC2中的存在表明，PRC2可能在异染色质介导的沉默中起着广泛的作用。
Enhancer of Zeste [E(z)] is a Polycomb-group transcriptional repressor and one of the founding members of the family of SET domain-containing proteins. Several SET-domain proteins possess intrinsic histone methyltransferase (HMT) activity. However, recombinant E(z) protein was found to be inactive in a HMT assay. Here we report the isolation of a multiprotein E(z) complex that contains extra sex combs, suppressor of zeste-12 [Su(z)12], and the histone binding proteins RbAp46/RbAp48. This complex, which we termed Polycomb repressive complex (PRC) 2, possesses HMT activity with specificity for Lys 9 (K9) and Lys 27 (K27) of histone H3. The HMT activity of PRC2 is dependent on an intact SET domain in the E(z) protein. We hypothesize that transcriptional repression by the E(z) protein involves methylation-dependent recruitment of PRC1. The presence of Su(z)12, a strong suppressor of position effect variegation, in PRC2 suggests that PRC2 may play a widespread role in heterochromatin-mediated silencing.