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Constitutively bound CTCF sites maintain 3D chromatin architecture and long-range epigenetically regulated domains

Citation

Khoury, A and Achinger-Kawecka, J and Bert, SA and Smith, GC and French, HJ and Luu, P-L and Peters, TJ and Du, Q and Parry, AJ and Valdes-Mora, F and Taberlay, PC and Stirzaker, C and Statham, AL and Clark, SJ, Constitutively bound CTCF sites maintain 3D chromatin architecture and long-range epigenetically regulated domains, Nature Communications, 11, (1) pp. 1-13. ISSN 2041-1723 (2020) [Refereed Article]


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Copyright 2020 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

DOI: doi:10.1038/s41467-019-13753-7

Abstract

The architectural protein CTCF is a mediator of chromatin conformation, but how CTCF binding to DNA is orchestrated to maintain long-range gene expression is poorly understood. Here we perform RNAi knockdown to reduce CTCF levels and reveal a shared subset of CTCF-bound sites are robustly resistant to protein depletion. The 'persistent' CTCF sites are enriched at domain boundaries and chromatin loops constitutive to all cell types. CRISPR-Cas9 deletion of 2 persistent CTCF sites at the boundary between a long-range epigenetically active (LREA) and silenced (LRES) region, within the Kallikrein (KLK) locus, results in concordant activation of all 8 KLK genes within the LRES region. CTCF genome-wide depletion results in alteration in Topologically Associating Domain (TAD) structure, including the merging of TADs, whereas TAD boundaries are not altered where persistent sites are maintained. We propose that the subset of essential CTCF sites are involved in cell-type constitutive, higher order chromatin architecture.

Item Details

Item Type:Refereed Article
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Epigenetics (incl. genome methylation and epigenomics)
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the biological sciences
UTAS Author:Taberlay, PC (Associate Professor Phillippa Taberlay)
ID Code:138624
Year Published:2020
Web of Science® Times Cited:16
Deposited By:Medicine
Deposited On:2020-04-20
Last Modified:2021-04-15
Downloads:9 View Download Statistics

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