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

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Khoury, A, Achinger-Kawecka, J, Bert, SA, Smith, GC, French, HJ, Luu, PL, Peters, TJ, Du, Q, Parry, AJ, Valdes-Mora, F, Taberlay, PC ORCID: 0000-0002-5298-8730, Stirzaker, C, Statham, AL and Clark, SJ 2020 , 'Constitutively bound CTCF sites maintain 3D chromatin architecture and long-range epigenetically regulated domains' , Nature Communications, vol. 11, no. 1 , doi: 10.1038/s41467-019-13753-7.

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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 Type: Article
Authors/Creators:Khoury, A and Achinger-Kawecka, J and Bert, SA and Smith, GC and French, HJ and Luu, PL 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
Journal or Publication Title: Nature Communications
Publisher: Nature Pub. Group
ISSN: 2041-1723
DOI / ID Number: 10.1038/s41467-019-13753-7
Copyright Information:

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

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