中国科技核心期刊
CN:31-1600/Q
ISSN:1004-0374
2018基因编辑学术研讨会      关于有网站冒充本刊网站的声明
《生命科学》 2017, 29(10): 968-976
细胞命运转化中的染色质重塑及其表观遗传调控机制
江赐忠*,高绍荣*
(同济大学生命科学与技术学院,上海市信号转导与疾病研究重点实验室,上海 200092)
摘 要:染色质重塑是重要的表观遗传调控机制,参与调控许多重要生物过程,但细胞命运转化中染色质变化模式及其调控机制并不清楚。围绕这一问题,江赐忠和高绍荣实验室研究了小鼠体细胞重编程及人胚胎干细胞(ESC) 定向分化成神经外胚层细胞(NEC) 中染色质重塑及其作用机制,取得一系列前沿性进展:揭示体细胞重编程中发生精确的核小体重塑,使之获得与ESC 没有差别的染色质结构;绘制体细胞重编程中核心全能性转录因子Oct4 的动态结合靶点与关键组蛋白修饰变化的分子路线图,及其两者互作对全能性获得与维持的调控机制;发现人ESC 向NEC 分化中,紧挨转录起始位点上游的核小体缺失区发生核小体丢失,激活NEC 相关基因,组蛋白乙酰基转移酶KAT2B 增加H3K9ac 信号来招募转录因子Sox2 结合到
    NEC 特异靶点激活靶点基因,促进NEC 分化。这些成果极大提高人们对细胞命运转化中染色质重塑及其表观遗传调控机制的认识。
 
Chromatin remodeling and its epigenetic regulatory mechanisms in cell fate transition
JIANG Ci-Zhong*, GAO Shao-Rong*
(Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China)
Abstract: Chromatin remodeling is an important epigenetic regulatory mechanism, and takes part in controlling many biological processes. However, the pattern and the functions of chromatin remodeling in cell fate transition remain enigmatic. To address this issue, we studied chromatin remodeling in mouse somatic cell reprograming and the differentiation of human embryonic cells (ESC) into neuroectodermal cells (NEC), respectively, and achieved a series of progress. The results show that accurate nucleosome remodeling takes place and results in a chromatin structure in iPSC highly similar to that in ESC. The core pluripotency factor Oct4 plays pivotal roles in somatic reprograming. We depicted the molecular roadmap of dynamic Oct4 binding and key histone modification changes in the course of somatic reprograming, and revealed the functions of their interactions in gain and maintenance of pluripotency. In the process of human ESC differentiating to NEC, we found that nucleosome eviction occurs in the nucleosome depletion regions right upstream of transcription start sites and activates these NEC-related genes. Acetyltransferase KAT2B deposits H3K9ac signal to recruit the transcription factor Sox2 binding to the target sites specific in NEC and activate the target genes, therefore facilitating the differentiation of NEC. These findings greatly improve our understanding of chromatin remodeling in cell fate transition and its associated epigenetic regulatory roles.
 
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