Histone deacetylation promotes mouse neural induction by restricting Nodal-dependent mesendoderm fate
Histone deacetylation promotes mouse neural induction by restricting Nodal-dependent mesendoderm fate
复制标题
组蛋白脱乙酰化通过限制Nodal依赖性中内胚层命运促进小鼠神经诱导
DOI：
10.1038/ncomms7830
复制
发表时间：
2015-04-01
影响因子：
16.6
通讯作者：
Jing, Naihe
中科院分区：
文献类型：
--
作者：
Liu, Pingyu;Dou, Xiaoyang;Jing, Naihe
Cell fate determination requires the cooperation between extrinsic signals and intrinsic molecules including transcription factors as well as epigenetic regulators. Nevertheless, how neural fate commitment is regulated by epigenetic modifications remains largely unclear. Here we show that transient histone deacetylation at epiblast stage promotes neural differentiation of mouse embryonic stem cells (mESCs). Histone deacetylase 1 (HDAC1) deficiency in mESCs partially phenocopies the inhibition of histone deacetylation in vitro, and displays reduced incorporation into neural tissues in chimeric mouse embryos in vivo. Mechanistic studies show that Nodal, which is repressed by histone deacetylation, is a direct target of HDAC1. Furthermore, the inhibition of histone deacetylation in the anterior explant of mouse embryos at E7.0 leads to Nodal activation and neural development repression. Thus, our study reveals an intrinsic mechanism that epigenetic histone deacetylation ensures neural fate commitment by restricting Nodal signalling in murine anterior epiblast ex vivo and mESC in vitro.
