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

Lando, David / Ma, Xiaoyan / Cao, Yang / Jartseva, Aleksandra / Stevens, Tim J / Boucher, Wayne / Reynolds, Nicola / Montibus, Bertille / Hall, Dominic / Lackner, Andreas / Ragheb, Ramy / Leeb, Martin / Hendrich, Brian D / Laue, Ernest D

Molecular cell

2024  Volume 84, Issue 8, Page(s) 1406–1421.e8

Abstract: 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 ... ...

Abstract 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.
MeSH term(s) Mice ; Animals ; Mouse Embryonic Stem Cells/metabolism ; Regulatory Sequences, Nucleic Acid ; Embryonic Stem Cells/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Chromatin/genetics ; Chromatin/metabolism ; Enhancer Elements, Genetic
Chemical Substances Transcription Factors ; Chromatin
Language English
Publishing date 2024-03-14
Publishing country United States
Document type Journal Article
ZDB-ID 1415236-8
ISSN 1097-4164 ; 1097-2765
ISSN (online) 1097-4164
ISSN 1097-2765
DOI 10.1016/j.molcel.2024.02.015
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