HPC3 is a new human polycomb orthologue that interacts and associates with RING1 and Bmi1 and Has transcriptional repression properties
HPC3 is a new human polycomb orthologue that interacts and associates with RING1 and Bmi1 and Has transcriptional repression properties
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DOI：
10.1074/jbc.m001835200
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发表时间：
2000-09-15
影响因子：
4.8
通讯作者：
Freemont, PS
中科院分区：
文献类型：
--
作者：
Bárdos, JI;Saurin, AJ;Freemont, PS
多梳蛋白组（PcG）蛋白最初在果蝇中被描述为在整个发育过程中以稳定且可遗传的方式维持Hox/同源异型基因转录抑制状态的因子。最近已鉴定出越来越多与果蝇PcG蛋白相关的脊椎动物基因，包括两个多梳同源物Pc2和M33。PcG蛋白形成多蛋白复合物，称为PcG小体，据认为它们通过改变染色质结构来抑制转录。在此我们报道HPC3（人类多梳3）的鉴定和特性，它是一种在以人类RING1为诱饵的酵母双杂交筛选中分离出的新型PcG蛋白。HPC3与果蝇Pc以及脊椎动物Pc2和M33显示出很强的序列相似性，特别是在染色质结构域和C - 盒内。先前的研究表明M33和人类Pc2（HPC2）能够与RING1相互作用，并且我们在此表明HPC3也与RING1结合。这种相互作用依赖于HPC3的C - 盒，但仅部分依赖于RING1的环指结构。与HPC2不同，HPC3与RING1的相互作用仅在体内观察到RING1的共价修饰形式时才存在。HPC3还与人类PcG小体中的其他PcG蛋白共定位。与它作为PcG成员的角色一致，当HPC3通过异源DNA结合域靶向一个报告基因时，它能够作为一种长距离转录沉默子起作用。综上所述，这些数据表明HPC3是一个大型多蛋白复合物的一部分，该复合物还包含其他PcG蛋白，并参与转录活性的抑制。
Polycomb group (PcG) proteins were first described in Drosophila as factors responsible for maintaining the transcriptionally repressed state of Hox/homeotic genes in a stable and heritable manner throughout development. A growing number of vertebrate genes related to the Drosophila PcG proteins have recently been identified, including two Polycomb orthologues, Pc2 and M33. PcG proteins form multiprotein complexes, termed PcG bodies, that are thought to repress transcription by altering chromatin structure. Here we report the identification and characterization of HPC3 (human Polycomb 3), a novel PcG protein isolated in a yeast two-hybrid screen using human RING1 as bait. HPC3 shows strong sequence similarity to Drosophila Pc and also to vertebrate Pc2 and M33, particularly within the chromodomain and C-box, Previous studies indicate that M33 and human Pc2 (HPC2) can interact with RING1, and we show here that HPC3 also binds to RING1. This interaction is dependent upon the HPC3 C-box but, only partially on the RING finger of RING1, In contrast to HPC2, HPC3 interactions with RING1 are only observed in vivo with covalently modified forms of RING1. HPC3 also colocalizes with other PcG proteins in human PcG bodies. Consistent with its role as a PcG member, HPC3 is able to act as a long range transcriptional silencer when targeted to a reporter gene by a heterologous DNA-binding domain. Taken together, these data suggest that HPC3 is part of a large multiprotein complex that also contains other PcG proteins and is involved in repression of transcriptional activity.