CTCF functions as an insulator for somatic genes and a chromatin remodeler for pluripotency genes during reprogramming

Song，Yawei1,2,3,4; Liang，Zhengyu5; Zhang，Jie1,2,3,4,6; Hu，Gongcheng1,2,3,4; Wang，Juehan1,2,3,4,6; Li，Yaoyi1,2,3,4; Guo，Rong1,2,3,4,6; Dong，Xiaotao1,2,3,4; Babarinde，Isaac A.8; Ping，Wangfang1,2,3,4,6; Sheng，Ying Liang1,2,3,4,7; Li，Huanhuan1; Chen，Zhaoming1,2; Gao，Minghui1; Chen，Yang9; Shan，Ge7; Zhang，Michael Q.9,10; Hutchins，Andrew P.8; Fu，Xiang Dong5; Yao，Hongjie1,2,3,4,6

2022-04-05

10.1016/j.celrep.2022.110626

Cell Reports   影响因子和分区

2211-1247

2211-1247

CTCF mediates chromatin insulation and long-distance enhancer-promoter (EP) interactions; however, little is known about how these regulatory functions are partitioned among target genes in key biological processes. Here, we show that Ctcf expression is progressively increased during induced pluripotency. In this process, CTCF first functions as a chromatin insulator responsible for direct silencing of the somatic gene expression program and, interestingly, elevated Ctcf expression next ensures chromatin accessibility and contributes to increased EP interactions for a fraction of pluripotency-associated genes. Therefore, CTCF functions in a context-specific manner to modulate the 3D genome to enable cellular reprogramming. We further discover that these context-specific CTCF functions also enlist SMARCA5, an imitation switch (ISWI) chromatin remodeler, together rewiring the epigenome to facilitate cell-fate switch. These findings reveal the dual functions of CTCF in conjunction with a key chromatin remodeler to drive reprogramming toward pluripotency.

chromatin accessibility chromatin insulation CP: Molecular biology CP: Stem cell research CTCF enhancer-promoter interactions reprogramming SMARCA5

SCI

英语

其他

Guangzhou Regenerative Medicine and Health Guangdong Laboratory[2018GZR110104007];Science and Technology Planning Project of Guangdong Province[2019A050510004];Science and Technology Planning Project of Guangdong Province[2019A1515110028];Science and Technology Planning Project of Guangdong Province[2019B020234004];Science and Technology Planning Project of Guangdong Province[2020B1212060052];China Postdoctoral Science Foundation[2020M682946];National Key Research and Development Program of China[2021YFA1100300];National Natural Science Foundation of China[31925009];National Natural Science Foundation of China[32000424];National Natural Science Foundation of China[32100462];National Natural Science Foundation of China[81902885];National Natural Science Foundation of China[U21A20195];Chinese Academy of Sciences[XDA16010502];

Cell Biology

Cell Biology

WOS:000787345400005

CELL PRESS

2-s2.0-85127498852

Scopus

1.CAS Key Laboratory of Regenerative Biology,Joint School of Life Sciences,Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou Medical University,Guangzhou,510530,China
2.Bioland Laboratory (Guangzhou Regenerative Medicine and Health GuangDong Laboratory),Guangzhou,510005,China
3.Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine,GIBH-CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine,State Key Laboratory of Respiratory Disease,Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou,510530,China
4.Institute of Stem Cell and Regeneration,Chinese Academy of Sciences,Beijing,100101,China
5.Department of Cellular and Molecular Medicine,Institute of Genomic Medicine,University of California,San Diego,La Jolla,92093-0651,United States
6.University of Chinese Academy of Sciences,Beijing,100049,China
7.Department of Life Sciences and Medicine,University of Science and Technology of China,Hefei,230027,China
8.Department of Biology,School of Life Sciences,Southern University of Science and Technology,Shenzhen,518055,China
9.MOE Key Laboratory of Bioinformatics,Bioinformatics Division and Center for Synthetic & Systems Biology,BNRist,School of Medicine,Tsinghua University,Beijing,100084,China
10.Department of Biological Sciences,Center for Systems Biology,The University of Texas,Richardson,75080-3021,United States

Song，Yawei,Liang，Zhengyu,Zhang，Jie,et al. CTCF functions as an insulator for somatic genes and a chromatin remodeler for pluripotency genes during reprogramming[J]. Cell Reports,2022,39(1).

Song，Yawei.,Liang，Zhengyu.,Zhang，Jie.,Hu，Gongcheng.,Wang，Juehan.,...&Yao，Hongjie.(2022).CTCF functions as an insulator for somatic genes and a chromatin remodeler for pluripotency genes during reprogramming.Cell Reports,39(1).

Song，Yawei,et al."CTCF functions as an insulator for somatic genes and a chromatin remodeler for pluripotency genes during reprogramming".Cell Reports 39.1(2022).