Kdm2b Regulates Somatic Reprogramming through Variant PRC1 Complex-Dependent Function
Kdm2b Regulates Somatic Reprogramming through Variant PRC1 Complex-Dependent Function
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Kdm2b 通过变体 PRC1 复合体依赖性功能调节体细胞重编程
DOI：
10.1016/j.celrep.2017.10.091
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发表时间：
2017-11-21
期刊：
影响因子：
8.8
通讯作者：
Chen, Jiekai
中科院分区：
文献类型：
--
作者：
Zhou, Zhiwei;Yang, Xuejie;Chen, Jiekai
Polycomb suppression complex 1 （PRC1）在细胞命运决定中起着重要作用。最近的研究发现，哺乳动物PRC1的组成特别多样和复杂；然而，对于这些变体PRC1复合物在细胞命运决定中的功能后果知之甚少。在这里，我们发现Kdm2b通过向CpG岛（cgi）募集变体PRC1复合体（PRC1.1）来促进oct4诱导的体细胞重编程。此外，我们发现骨形态发生蛋白（BMP）选择性地抑制Oct4/ kdm2b诱导的体细胞重编程。从机制上讲，BMP-SMAD通路减弱与发育相关基因的PRC1.1占据和H2AK119泛素化，导致中胚层因子如Sox17的表达，从而抑制体细胞重编程。这些观察结果表明，PRC1.1参与多能性的建立，并确定BMP4信号作为PRC1.1功能的调节剂。
Polycomb repressive complex 1 (PRC1) plays essential roles in cell-fate determination. Recent studies have found that the composition of mammalian PRC1 is particularly varied and complex; however, little is known about the functional consequences of these variant PRC1 complexes on cell-fate determination. Here, we show that Kdm2b promotes Oct4-induced somatic reprogramming through recruitment of a variant PRC1 complex (PRC1.1) to CpG islands (CGIs). Furthermore, we find that bone morphogenetic protein (BMP) represses Oct4/Kdm2b-induced somatic reprogramming selectively. Mechanistically, BMP-SMAD pathway attenuates PRC1.1 occupation and H2AK119 ubiquitination at genes linked to development, resulting in the expression of mesendodermal factors such as Sox17 and a consequent suppression of somatic reprogramming. These observations reveal that PRC1.1 participates in the establishment of pluripotency and identify BMP4 signaling as a modulator of PRC1.1 function.