重编程
细胞生物学
染色质
异染色质
染色质重塑
KLF4公司
组蛋白
生物
磷酸化
表观遗传学
化学
作者
Guangsuo Xing,Zichao Liu,Huang Luyuan,Danyun Zhao,Tao Wang,Hao Yuan,Yi Wu,Linpeng Li,Qi Long,Yanshuang Zhou,Zhihong Hao,Yang Liu,Jianghuan Lu,Shiting Li,Jieying Zhu,Bo Wang,Junwei Wang,Jing Liu,Jiekai Chen,Duanqing Pei,Xingguo Liu,Keshi Chen
标识
DOI:10.1038/s41418-021-00902-z
摘要
Somatic cell reprogramming is an ideal model for studying epigenetic regulation as it undergoes dramatic chromatin remodeling. However, a role for phosphorylation signaling in chromatin protein modifications for reprogramming remains unclear. Here, we identified mitogen-activated protein kinase kinase 6 (Mkk6) as a chromatin relaxer and found that it could significantly enhance reprogramming. The function of Mkk6 in heterochromatin loosening and reprogramming requires its kinase activity but does not depend on its best-known target, P38. We identified Gatad2b as a novel target of Mkk6 phosphorylation that acts downstream to elevate histone acetylation levels and loosen heterochromatin. As a result, Mkk6 over-expression facilitates binding of Sox2 and Klf4 to their targets and promotes pluripotency gene expression during reprogramming. Our studies not only reveal an Mkk phosphorylation mediated modulation of chromatin status in reprogramming, but also provide new rationales to further investigate and improve the cell fate determination processes.
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