Ubiquitination-Independent Repression of PRC1 Targets during Neuronal Fate Restriction in the Developing Mouse Neocortex
Ubiquitination-Independent Repression of PRC1 Targets during Neuronal Fate Restriction in the Developing Mouse Neocortex
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DOI：
10.1016/j.devcel.2018.11.018
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发表时间：
2018-12-17
影响因子：
11.8
通讯作者：
Gotoh, Yukiko
中科院分区：
文献类型：
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作者：
Tsuboi, Masafumi;Kishi, Yusuke;Gotoh, Yukiko
Polycomb suppression complex (PRC) 1通过组蛋白H2A的单泛素化（Ub）维持发育基因处于平衡状态。尽管也有人提出了PRC1的不依赖于ub的功能，但目前尚不清楚PRC1的依赖于ub和不依赖于ub的功能在发育背景下是否存在差异。在这里，我们发现PRC1的核心成分环1b的E3泛素连接酶活性对于神经源性（早期）神经干或祖细胞（npc）中关键神经元基因的暂时抑制是必要的，但对于星形胶质源性（晚期）npc中与神经源性潜能丧失相关的这些基因的持续抑制是必不可少的。我们的研究结果还表明，NuRD/MBD3复合物的组蛋白去乙酰化酶（HDAC）活性和phc2依赖的PRC1聚类是PRC1从ub依赖功能转变为不依赖功能的必要条件。综上所述，这些结果表明，PRC1不依赖于ub的抑制模式在哺乳动物细胞命运限制期间的发育中起着关键作用。
Polycomb repressive complex (PRC) 1 maintains developmental genes in a poised state through monoubiquitination (Ub) of histone H2A. Although Ub-independent functions of PRC1 have also been suggested, it has remained unclear whether Ub-dependent and -independent functions of PRC1 operate differentially in a developmental context. Here, we show that the E3 ubiquitin ligase activity of Ring1B, a core component of PRC1, is necessary for the temporary repression of key neuronal genes in neurogenic (early-stage) neural stem or progenitor cells (NPCs) but is dispensable for the persistent repression of these genes associated with the loss of neurogenic potential in astrogliogenic (late-stage) NPCs. Our results also suggest that histone deacetylase (HDAC) activity of the NuRD/MBD3 complex and Phc2-dependent PRC1 clustering are necessary for the transition from the Ub-dependent to -independent function of PRC1. Together, these results indicate that Ub-independent mode of repression by PRC1 plays a key role in mammalian development during cell fate restriction.