CTCF mediates dosage- and sequence-context-dependent transcriptional insulation by forming local chromatin domains

Item Type:	Article
Title:	CTCF mediates dosage- and sequence-context-dependent transcriptional insulation by forming local chromatin domains
Creators Name:	Huang, H. and Zhu, Q. and Jussila, A. and Han, Y. and Bintu, B. and Kern, C. and Conte, M. and Zhang, Y. and Bianco, S. and Chiariello, A.M. and Yu, M. and Hu, R. and Tastemel, M. and Juric, I. and Hu, M. and Nicodemi, M. and Zhuang, X. and Ren, B.
Abstract:	Insulators play a critical role in spatiotemporal gene regulation in animals. The evolutionarily conserved CCCTC-binding factor (CTCF) is required for insulator function in mammals, but not all of its binding sites act as insulators. Here we explore the sequence requirements of CTCF-mediated transcriptional insulation using a sensitive insulator reporter in mouse embryonic stem cells. We find that insulation potency depends on the number of CTCF-binding sites in tandem. Furthermore, CTCF-mediated insulation is dependent on upstream flanking sequences at its binding sites. CTCF-binding sites at topologically associating domain boundaries are more likely to function as insulators than those outside topologically associating domain boundaries, independently of binding strength. We demonstrate that insulators form local chromatin domain boundaries and weaken enhancer–promoter contacts. Taken together, our results provide genetic, molecular and structural evidence connecting chromatin topology to the action of insulators in the mammalian genome.
Keywords:	Binding Sites, CCCTC-Binding Factor, Chromatin, Gene Expression Regulation, Genetic Enhancer Elements, Genetic Promoter Regions, Genetic Transcription, Insulator Elements, Mouse Embryonic Stem Cells, Protein Binding, Animals, Mice
Source:	Nature Genetics
ISSN:	1061-4036
Publisher:	Nature Publishing Group
Volume:	53
Number:	7
Page Range:	1064-1074
Date:	July 2021
Additional Information:	Copyright © The Author(s), under exclusive licence to Springer Nature America, Inc. 2021
Official Publication:	https://doi.org/10.1038/s41588-021-00863-6
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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