期刊
CELL REPORTS
卷 20, 期 13, 页码 3236-3247出版社
CELL PRESS
DOI: 10.1016/j.celrep.2017.09.011
关键词
-
类别
资金
- NIH [P50-HG007735]
- California Institute for Regenerative Medicine [RB5-07466, RB4-05763]
- Howard Hughes Medical Institute
- New York Stem Cell Foundation-Robertson Award
- National Science Foundation
- Agency for Science, Technology, and Research
How transcription factors (TFs) reprogram one cell lineage to another remains unclear. Here, we define chromatin accessibility changes induced by the proneural TF Ascl1 throughout conversion of fibroblasts into induced neuronal (iN) cells. Thousands of genomic loci are affected as early as 12 hr after Ascl1 induction. Surprisingly, over 80% of the accessibility changes occur between days 2 and 5 of the 3-week reprogramming process. This chromatin switch coincides with robust activation of endogenous neuronal TFs and nucleosome phasing of neuronal promoters and enhancers. Subsequent morphological and functional maturation of iN cells is accomplished with relatively little chromatin reconfiguration. By integrating chromatin accessibility and transcriptome changes, we built a network model of dynamic TF regulation during iN cell reprogramming and identified Zfp238, Sox8, and Dlx3 as key TFs downstream of Ascl1. These results reveal a singular, coordinated epigenomic switch during direct reprogramming, in contrast to stepwise cell fate transitions in development.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据