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hnRNPK Recruits PCGF3/5-PRC1 to the Xist RNA B-Repeat to Establish Polycomb-Mediated Chromosomal Silencing
Molecular Cell ( IF 14.5 ) Pub Date : 2017-12-07
Greta Pintacuda, Guifeng Wei, Chloë Roustan, Burcu Anil Kirmizitas, Nicolae Solcan, Andrea Cerase, Alfredo Castello, Shabaz Mohammed, Benoît Moindrot, Tatyana B. Nesterova, Neil Brockdorff

The Polycomb-repressive complexes PRC1 and PRC2 play a key role in chromosome silencing induced by the non-coding RNA Xist. Polycomb recruitment is initiated by the PCGF3/5-PRC1 complex, which catalyzes chromosome-wide H2A lysine 119 ubiquitylation, signaling recruitment of other PRC1 complexes, and PRC2. However, the molecular mechanism for PCGF3/5-PRC1 recruitment by Xist RNA is not understood. Here we define the Xist RNA Polycomb Interaction Domain (XR-PID), a 600 nt sequence encompassing the Xist B-repeat element. Deletion of XR-PID abolishes Xist-dependent Polycomb recruitment, in turn abrogating Xist-mediated gene silencing and reversing Xist-induced chromatin inaccessibility. We identify the RNA-binding protein hnRNPK as the principal XR-PID binding factor required to recruit PCGF3/5-PRC1. Accordingly, synthetically tethering hnRNPK to Xist RNA lacking XR-PID is sufficient for Xist-dependent Polycomb recruitment. Our findings define a key pathway for Polycomb recruitment by Xist RNA, providing important insights into mechanisms of chromatin modification by non-coding RNA.



中文翻译:

hnRNPK在Xist RNA B重复中募集PCGF3 / 5-PRC1以建立多梳介导的染色体沉默

阻聚复合物PRC1和PRC2在非编码RNA Xist诱导的染色体沉默中起关键作用。聚梳募集由PCGF3 / 5-PRC1复合物启动,该复合物催化整个染色体的H2A赖氨酸119泛素化,表明其他PRC1复合物和PRC2募集。但是,尚不清楚通过Xist RNA募集PCGF3 / 5-PRC1的分子机制。在这里,我们定义了Xist RNA多梳相互作用域(XR-PID),这是一个包含Xist B重复元素的600 nt序列。XR-PID的删除废除了Xist依赖的Polycomb募集,从而废除了Xist介导的基因沉默并逆转Xist诱导的染色质不可及性。我们确定RNA结合蛋白hnRNPK为招募PCGF3 / 5-PRC1所需的主要XR-PID结合因子。因此,将hnRNPK人工绑定到缺少XR-PID的Xist RNA上足以进行Xist依赖的Polycomb募集。我们的发现确定了Xist RNA募集Polycomb的关键途径,提供了对非编码RNA染色质修饰机制的重要见解。

更新日期:2017-12-10
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