UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Enhancer accessibility and CTCF occupancy underlie asymmetric TAD architecture and cell type specific genome topology

Barrington, C; Georgopoulou, D; Pezic, D; Varsally, W; Herrero, J; Hadjur, S; (2019) Enhancer accessibility and CTCF occupancy underlie asymmetric TAD architecture and cell type specific genome topology. Nature Communications , 10 , Article 2908. 10.1038/s41467-019-10725-9. Green open access

[img]
Preview
Text
s41467-019-10725-9.pdf - Published version

Download (4MB) | Preview

Abstract

Cohesin and CTCF are master regulators of genome topology. How these ubiquitous proteins contribute to cell-type specific genome structure is poorly understood. Here, we explore quantitative aspects of topologically associated domains (TAD) between pluripotent embryonic stem cells (ESC) and lineage-committed cells. ESCs exhibit permissive topological configurations which manifest themselves as increased inter- TAD interactions, weaker intra-TAD interactions, and a unique intra-TAD connectivity whereby one border makes pervasive interactions throughout the domain. Such ‘stripe’ domains are associated with both poised and active chromatin landscapes and transcription is not a key determinant of their structure. By tracking the developmental dynamics of stripe domains, we show that stripe formation is linked to the functional state of the cell through cohesin loading at lineage-specific enhancers and developmental control of CTCF binding site occupancy. We propose that the unique topological configuration of stripe domains represents a permissive landscape facilitating both productive and opportunistic gene regulation and is important for cellular identity.

Type: Article
Title: Enhancer accessibility and CTCF occupancy underlie asymmetric TAD architecture and cell type specific genome topology
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41467-019-10725-9
Publisher version: https://doi.org/10.1038/s41467-019-10725-9
Language: English
Additional information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: https://discovery.ucl.ac.uk/id/eprint/10077871
Downloads since deposit
25Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item