Role for the MOV10 RNA helicase in polycomb-mediated repression of the INK4a tumor suppressor.

Role for the MOV10 RNA helicase in polycomb-mediated repression of the INK4a tumor suppressor.
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DOI:
10.1038/nsmb.1824
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发表时间:
2010-07
影响因子:
16.8
通讯作者:
--
中科院分区:
生物学1区
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--
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一些证据表明,非编码RNA在Polycomb组(PcG)蛋白的转录抑制中发挥作用,但确切的机制仍不清楚。在这里,我们表明,MOV10,一个假定的RNA解旋酶先前参与转录后基因沉默,共纯化和相互作用的Polycomb抑制复合物1(PRC1)从人类细胞的组件。内源性MOV10大部分是核的,并且一部分以RNA依赖的方式与染色质结合。shRNA介导的人成纤维细胞中MOV10的敲低导致INK4a肿瘤抑制因子的上调,INK4a肿瘤抑制因子是PcG介导的抑制的已知靶点,伴随着PRC1蛋白从基因座的解离和组蛋白H3在赖氨酸27(H3K27me3)上的三甲基化的减少。我们的研究结果不仅促使我们重新评估MOV10在其他环境中的作用,还表明它直接参与了PcG复合物的转录沉默。
Several lines of evidence point to a role for non-coding RNA in transcriptional repression by Polycomb group (PcG) proteins but the precise mechanism remains unclear. Here we show that MOV10, a putative RNA helicase previously implicated in post-transcriptional gene silencing, co-purifies and interacts with components of Polycomb-repressive complex 1 (PRC1) from human cells. Endogenous MOV10 is mostly nuclear and a proportion associates with chromatin in an RNA-dependent manner. ShRNA-mediated knockdown of MOV10 in human fibroblasts leads to up-regulation of the INK4a tumor suppressor, a known target of PcG-mediated repression, accompanied by dissociation of PRC1 proteins from the locus and a reduction in trimethylation of histone H3 on lysine 27 (H3K27me3). As well as prompting reassessment of MOV10's role in other settings, our findings suggest that it is directly involved in transcriptional silencing by PcG complexes.
Polycomb 在衰老过程中介导 INK4a/ARF 位点的表观遗传沉默和复制计时。
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