1. CTCF functions as an insulator for somatic genes and a chromatin remodeler for pluripotency genes during reprogramming.
- Author
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Song Y, Liang Z, Zhang J, Hu G, Wang J, Li Y, Guo R, Dong X, Babarinde IA, Ping W, Sheng YL, Li H, Chen Z, Gao M, Chen Y, Shan G, Zhang MQ, Hutchins AP, Fu XD, and Yao H
- Subjects
- Animals, Humans, Mice, Promoter Regions, Genetic, CCCTC-Binding Factor genetics, CCCTC-Binding Factor metabolism, Cellular Reprogramming genetics, Chromatin, Enhancer Elements, Genetic genetics
- Abstract
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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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