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Nature:AUTS2在神经疾病中的作用

摘要 : 多梳类蛋白(它们在发育过程中维持基因抑制)包含两种主要复合物(PRC1和PRC2),具有截然不同的酶活性。一些PRC1复合物与“自闭症易感性候选基因-2”(AUTS2)有关,这是在神经疾病中经常被破坏的一个基因。

 多梳类蛋白(它们在发育过程中维持基因抑制)包含两种主要复合物(PRC1和PRC2),具有截然不同的酶活性。一些PRC1复合物与“自闭症易感性候选基因-2”(AUTS2)有关,这是在神经疾病中经常被破坏的一个基因。在这项研究中,Danny Reinberg及同事发现,AUTS2赋予PRC1一个出乎意料的转录激发功能, PRC1–AUTS2复合体调控神经基因。小鼠中枢神经系统中Auts2 位点的删除导致发育缺陷。正常脑发育期间AUTS2在调控PRC1活性中可能起一个关键作用。

nature13921-f2

原文标题:An AUTS2–Polycomb complex activates gene expression in the CNS

原文摘要:Naturally occurring variations of Polycomb repressive complex 1 (PRC1) comprise a core assembly of Polycomb group proteins and additional factors that include, surprisingly, autism susceptibility candidate 2 (AUTS2). Although AUTS2 is often disrupted in patients with neuronal disorders, the mechanism underlying the pathogenesis is unclear. We investigated the role of AUTS2 as part of a previously identified PRC1 complex (PRC1–AUTS2), and in the context of neurodevelopment. In contrast to the canonical role of PRC1 in gene repression, PRC1–AUTS2 activates transcription. Biochemical studies demonstrate that the CK2 component of PRC1–AUTS2 neutralizes PRC1 repressive activity, wheras AUTS2-mediated recruitment of P300 leads to gene activation. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) demonstrated that AUTS2 regulates neuronal gene expression through promoter association. Conditional targeting of Auts2in the mouse central nervous system (CNS) leads to various developmental defects. These findings reveal a natural means of subverting PRC1 activity, linking key epigenetic modulators with neuronal functions and diseases.

对应Nature杂志: 2014年12月18日Nature杂志精选

来源: Nature 浏览次数:140

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