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Transcriptional Pause Release Is a Rate-Limiting Step for Somatic Cell Reprogramming

发布日期:2014/10/20 11:25:47

期刊名称:Cell Stem Cell

期刊号:DOI: 10.1016/j.stem.2014.09.018

通迅作者:Miguel A. Esteban

作者单位:中科院广州生物医药与健康研究院

使用产品与服务:RNA-Seq

文章摘要:

Reactivation of the pluripotency network during somatic cell reprogramming by exogenous transcription factors involves chromatin remodelingand 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, whereas 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.

实验结果:




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