138624 - Constitutively bound CTCF sites.pdf (1.76 MB)
Constitutively bound CTCF sites maintain 3D chromatin architecture and long-range epigenetically regulated domains
journal contribution
posted on 2023-05-20, 13:46 authored by Khoury, A, Achinger-Kawecka, J, Bert, SA, Smith, GC, French, HJ, Luu, P-L, Peters, TJ, Du, Q, Parry, AJ, Valdes-Mora, F, Phillippa TaberlayPhillippa Taberlay, Stirzaker, C, Statham, AL, Clark, SJThe 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.
History
Publication title
Nature CommunicationsVolume
11Article number
54Number
54Pagination
1-13ISSN
2041-1723Department/School
Tasmanian School of MedicinePublisher
Nature Pub. GroupPlace of publication
United KingdomRights statement
Copyright 2020 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/Repository Status
- Open