摘要
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.
