State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Cell Death Differ. 2018 Feb;25(2):294-306. doi: 10.1038/cdd.2017.157. Epub 2017 Oct 6.
Astrocyte has crucial roles in the central nervous system and accumulating evidence has shown its core function for brain complexity, plasticity and cognition. However, the essential key factors in the precise regulation of astrocytic differentiation remain largely uncharacterized. Here, we identified that RNF20, an E3 ligase of H2BK120 in the mammalian system, regulates astrocyte production from neural precursor cells. RNF20 deficiency by shRNA knockdown or deletion in conditional knockout mice impairs the astrocytic differentiation. Overexpression of RNF20 promotes astrocytic differentiation and can rescue the astrocyte production deficiency caused by RNF20 disruption. Furthermore, we demonstrate that RNF20 functions cooperatively with acetyltransferase MOF to promote astrocytic generation. RNF20-mediated H2Bub1 cooperating with MOF-mediated H4K16ac activates the transcription of Stat3. Together, these data indicate RNF20 is a critical regulator of astrocytic production, which may contribute to the understanding of neurological disorders with glial dysgenesis.
星形胶质细胞在中枢神经系统中起着至关重要的作用，越来越多的证据表明其核心功能是大脑的复杂性、可塑性和认知。然而，星形胶质细胞分化的精确调控的关键因素在很大程度上仍未被描述。在这里，我们发现 RNF20，哺乳动物系统中 H2BK120 的 E3 连接酶，调节神经前体细胞向星形胶质细胞的产生。通过短发夹 RNA 敲低或条件性敲除小鼠中的缺失，RNF20 的缺乏会损害星形胶质细胞的分化。RNF20 的过表达促进星形胶质细胞的分化，并能挽救 RNF20 破坏引起的星形胶质细胞产生缺陷。此外，我们证明 RNF20 与乙酰转移酶 MOF 协同作用促进星形胶质细胞的产生。RNF20 介导的 H2Bub1 与 MOF 介导的 H4K16ac 共同激活 Stat3 的转录。总之，这些数据表明 RNF20 是星形胶质细胞产生的关键调节因子，这可能有助于理解伴有神经胶质发育不良的神经紊乱。
