Transcriptional pause release is a rate-limiting step for somatic cell reprogramming
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Transcriptional pause release is a rate-limiting step for somatic cell reprogramming. / Liu, Longqi; Xu, Yan; He, Minghui; Zhang, Meng; Cui, Fenggong; Lu, Leina; Yao, Mingze; Tian, Weihua; Benda, Christina; Zhuang, Qiang; Huang, Zhijian; Li, Wenjuan; Li, Xiangchun; Zhao, Ping; Fan, Wenxia; Luo, Zhiwei; Li, Yuan; Wu, Yasong; Hutchins, Andrew P; Wang, Dongye; Tse, Hung-Fat; Schambach, Axel; Frampton, Jon; Qin, Baoming; Bao, Xichen; Yao, Hongjie; Zhang, Biliang; Sun, Hao; Pei, Duanqing; Wang, Huating; Wang, Jun; Esteban, Miguel A.
I: Cell Stem Cell, Bind 15, Nr. 5, 06.11.2014, s. 574-88.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Transcriptional pause release is a rate-limiting step for somatic cell reprogramming
AU - Liu, Longqi
AU - Xu, Yan
AU - He, Minghui
AU - Zhang, Meng
AU - Cui, Fenggong
AU - Lu, Leina
AU - Yao, Mingze
AU - Tian, Weihua
AU - Benda, Christina
AU - Zhuang, Qiang
AU - Huang, Zhijian
AU - Li, Wenjuan
AU - Li, Xiangchun
AU - Zhao, Ping
AU - Fan, Wenxia
AU - Luo, Zhiwei
AU - Li, Yuan
AU - Wu, Yasong
AU - Hutchins, Andrew P
AU - Wang, Dongye
AU - Tse, Hung-Fat
AU - Schambach, Axel
AU - Frampton, Jon
AU - Qin, Baoming
AU - Bao, Xichen
AU - Yao, Hongjie
AU - Zhang, Biliang
AU - Sun, Hao
AU - Pei, Duanqing
AU - Wang, Huating
AU - Wang, Jun
AU - Esteban, Miguel A
N1 - Copyright © 2014 Elsevier Inc. All rights reserved.
PY - 2014/11/6
Y1 - 2014/11/6
N2 - 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, 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.
AB - 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, 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.
KW - Animals
KW - Base Sequence
KW - Cellular Reprogramming/genetics
KW - Cyclin-Dependent Kinase 9/metabolism
KW - Embryo, Mammalian/cytology
KW - Embryonic Stem Cells/cytology
KW - Fibroblasts/cytology
KW - Gene Expression Regulation
KW - Genome
KW - HEK293 Cells
KW - Humans
KW - Kinetics
KW - Kruppel-Like Factor 4
KW - Kruppel-Like Transcription Factors/metabolism
KW - Mice
KW - Molecular Sequence Data
KW - Nuclear Proteins/metabolism
KW - Pluripotent Stem Cells/cytology
KW - Positive Transcriptional Elongation Factor B/metabolism
KW - Promoter Regions, Genetic
KW - Protein Binding/genetics
KW - RNA Polymerase II/metabolism
KW - RNA-Binding Proteins
KW - Transcription Factors/metabolism
KW - Transcription, Genetic
U2 - 10.1016/j.stem.2014.09.018
DO - 10.1016/j.stem.2014.09.018
M3 - Journal article
C2 - 25312495
VL - 15
SP - 574
EP - 588
JO - Cell Stem Cell
JF - Cell Stem Cell
SN - 1934-5909
IS - 5
ER -
ID: 317433514