CTCF chromatin residence time controls three-dimensional genome organization, gene expression and DNA methylation in pluripotent cells

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• dc.contributor.author Soochit, Widia
• dc.contributor.author Stik, Grégoire
• dc.contributor.author Vidal, Enrique
• dc.contributor.author Graf, T. (Thomas)
• dc.contributor.author Galjart, Niels
• dc.date.accessioned 2021-09-10T07:17:57Z
• dc.date.issued 2021
• dc.description.abstract The 11 zinc finger (ZF) protein CTCF regulates topologically associating domain formation and transcription through selective binding to thousands of genomic sites. Here, we replaced endogenous CTCF in mouse embryonic stem cells with green-fluorescent-protein-tagged wild-type or mutant proteins lacking individual ZFs to identify additional determinants of CTCF positioning and function. While ZF1 and ZF8-ZF11 are not essential for cell survival, ZF8 deletion strikingly increases the DNA binding off-rate of mutant CTCF, resulting in reduced CTCF chromatin residence time. Loss of ZF8 results in widespread weakening of topologically associating domains, aberrant gene expression and increased genome-wide DNA methylation. Thus, important chromatin-templated processes rely on accurate CTCF chromatin residence time, which we propose depends on local sequence and chromatin context as well as global CTCF protein concentration.
• dc.format.mimetype application/pdf
• dc.identifier.citation Soochit W, Sleutels F, Stik G, Bartkuhn M, Basu S, Hernandez SC et al. CTCF chromatin residence time controls three-dimensional genome organization, gene expression and DNA methylation in pluripotent cells. Nat Cell Biol. 2021;23(8):881-93. DOI: 10.1038/s41556-021-00722-w
• dc.identifier.doi http://dx.doi.org/10.1038/s41556-021-00722-w
• dc.identifier.issn 1465-7392
• dc.identifier.uri http://hdl.handle.net/10230/48420
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Nat Cell Biol. 2021;23(8):881-93
• dc.rights © Springer Nature Publishing AG Soochit W, Sleutels F, Stik G, Bartkuhn M, Basu S, Hernandez SC et al. CTCF chromatin residence time controls three-dimensional genome organization, gene expression and DNA methylation in pluripotent cells. Nat Cell Biol. 2021;23(8):881-93. DOI: 10.1038/s41556-021-00722-w [http://dx.doi.org/10.1038/s41556-021-00722-w]
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.keyword Chromosome conformation capture-based methods
• dc.subject.keyword DNA metabolism
• dc.subject.keyword Embryonic stem cells
• dc.subject.keyword Nuclear organization
• dc.title CTCF chromatin residence time controls three-dimensional genome organization, gene expression and DNA methylation in pluripotent cells
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion