Enhancer-promoter interactions are reconfigured through the formation of long-range multiway hubs as mouse ES cells exit pluripotency.

Autor:	Lando D; Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK., Ma X; Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK., Cao Y; Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK., Jartseva A; Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK., Stevens TJ; MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK., Boucher W; Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK., Reynolds N; Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge CB2 0AW, UK., Montibus B; Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge CB2 0AW, UK., Hall D; Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK; Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge CB2 0AW, UK., Lackner A; Max Perutz Laboratories Vienna, University of Vienna, Vienna Biocenter, Vienna, Austria., Ragheb R; Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge CB2 0AW, UK., Leeb M; Max Perutz Laboratories Vienna, University of Vienna, Vienna Biocenter, Vienna, Austria., Hendrich BD; Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK; Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge CB2 0AW, UK. Electronic address: bdh24@cam.ac.uk., Laue ED; Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK; Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge CB2 0AW, UK. Electronic address: e.d.laue@bioc.cam.ac.uk.
Jazyk:	angličtina
Zdroj:	Molecular cell [Mol Cell] 2024 Apr 18; Vol. 84 (8), pp. 1406-1421.e8. Date of Electronic Publication: 2024 Mar 14.
DOI:	10.1016/j.molcel.2024.02.015
Abstrakt:	Enhancers bind transcription factors, chromatin regulators, and non-coding transcripts to modulate the expression of target genes. Here, we report 3D genome structures of single mouse ES cells as they are induced to exit pluripotency and transition through a formative stage prior to undergoing neuroectodermal differentiation. We find that there is a remarkable reorganization of 3D genome structure where inter-chromosomal intermingling increases dramatically in the formative state. This intermingling is associated with the formation of a large number of multiway hubs that bring together enhancers and promoters with similar chromatin states from typically 5-8 distant chromosomal sites that are often separated by many Mb from each other. In the formative state, genes important for pluripotency exit establish contacts with emerging enhancers within these multiway hubs, suggesting that the structural changes we have observed may play an important role in modulating transcription and establishing new cell identities. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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