西亚试剂 ：Transcriptional Pause Release Is a Rate-Limiting Step fo

发布时间：2025-06-04

Longqi Liu, Yan Xu, Minghui He, Meng Zhang, Fenggong Cui, Leina Lu, Mingze Yao, Weihua Tian, Christina Benda, Qiang Zhuang,Zhijian Huang, Wenjuan Li, Xiangchun Li, Ping Zhao, Wenxia Fan, Zhiwei Luo, Yuan Li, Yasong Wu, Andrew P. Hutchins, Dongye Wang,Hung-Fat Tse, Axel Schambach, Jon Frampton, Baoming Qin, Xichen Bao, Hongjie Yao, Biliang Zhang, Hao Sun, Duanqing Pei,Huating Wang, Jun Wang, Miguel A. Esteban

Reactivation of the pluripotency network during somatic cell reprogramming by exogenous transcription factors involves chromatin remodeling and the recruitment of RNA polymerase II (Pol II) to target loci. Here, we report that Pol II is engaged at pluripotency promoters in reprogramming but remains paused and inefficiently released. We also show that bromodomain-containing protein 4 (BRD4) stimulates productive transcriptional elongation of pluripotency genes by dissociating the pause release factor P-TEFb from an inactive complex containing HEXIM1. Consequently, BRD4 overexpression enhances reprogramming efficiency and HEXIM1 suppresses it, wheras Brd4 and Hexim1 knockdown do the opposite. We further demonstrate that the reprogramming factor KLF4 helps recruit P-TEFb to pluripotency promoters. Our work thus provides a mechanism for explaining the reactivation of pluripotency genes in reprogramming and unveils an unanticipated role for KLF4 in transcriptional pause release.以上资料由西亚试剂：http://www.xiyashiji.com/提供

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