HP1BP3, a Chromatin Retention Factor for Co-transcriptional MicroRNA Processing.
HP1BP3, a Chromatin Retention Factor for Co-transcriptional MicroRNA Processing.
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DOI：
10.1016/j.molcel.2016.06.014
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发表时间：
2016-08-04
期刊：
影响因子：
16
通讯作者：
Liu Q
中科院分区：
文献类型：
--
作者：
Liu H;Liang C;Kollipara RK;Matsui M;Ke X;Jeong BC;Wang Z;Yoo KS;Yadav GP;Kinch LN;Grishin NV;Nam Y;Corey DR;Kittler R;Liu Q
最近的研究表明，微处理器（Drosha-DGCR 8）复合物可以被募集到染色质中以催化哺乳动物细胞中初级microRNA（pri-miRNAs）的共转录加工。然而，共转录miRNA加工的分子机制知之甚少。在这里，我们发现HP 1BP 3，一种组蛋白H1样染色质蛋白，特异性地与微处理器相关联，并促进人类细胞中的全局miRNA生物合成。染色质免疫沉淀（ChIP）研究揭示了HP 1BP 3和Drosha的全基因组共定位以及HP 1BP 3依赖性Drosha与活跃转录的miRNA位点的结合。此外，HP 1BP 3特异性结合内源性pri-miRNA并促进Drosha/pri-miRNA在体内的结合。HP 1BP 3的敲低通过引起pri-miRNA从染色质的过早释放而损害pri-miRNA加工。综上所述，这些研究表明，HP 1BP 3通过新生pri-miRNA转录物的染色质保留促进共转录miRNA加工。这项工作显着扩展了H1家族蛋白质的功能库，并表明存在广泛的共转录miRNA加工的染色质保留因子。
Recent studies suggest that the Microprocessor (Drosha-DGCR8) complex can be recruited to chromatin to catalyze co-transcriptional processing of primary microRNAs (pri-miRNAs) in mammalian cells. However, the molecular mechanism of co-transcriptional miRNA processing is poorly understood. Here, we find that HP1BP3, a histone H1-like chromatin protein, specifically associates with the Microprocessor and promotes global miRNA biogenesis in human cells. Chromatin immunoprecipitation (ChIP) studies reveal genome-wide co-localization of HP1BP3 and Drosha and HP1BP3-dependent Drosha binding to actively transcribed miRNA loci. Moreover, HP1BP3 specifically binds endogenous pri-miRNAs and facilitates the Drosha/pri-miRNA association in vivo. Knockdown of HP1BP3 compromises pri-miRNA processing by causing premature release of pri-miRNAs from the chromatin. Taken together, these studies suggest that HP1BP3 promotes co-transcriptional miRNA processing via chromatin retention of nascent pri-miRNA transcripts. This work significantly expands the functional repertoire of the H1 family of proteins and suggests the existence of chromatin retention factors for widespread co-transcriptional miRNA processing.