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

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ID: 94076
2020
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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.
Reference Key
khoury2020constitutivelynature Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Khoury, Amanda;Achinger-Kawecka, Joanna;Bert, Saul A;Smith, Grady C;French, Hugh J;Luu, Phuc-Loi;Peters, Timothy J;Du, Qian;Parry, Aled J;Valdes-Mora, Fatima;Taberlay, Phillippa C;Stirzaker, Clare;Statham, Aaron L;Clark, Susan J;
Journal Nature communications
Year 2020
DOI
10.1038/s41467-019-13753-7
URL
Keywords
local adaptation phenotypic plasticity geometric morphometrics adaptive radiation common garden experiment ampullariidae differential fitness

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