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Global reorganisation of $\textit{cis}$-regulatory units upon lineage commitment of human embryonic stem cells

Published version
Peer-reviewed

Change log

Authors

Freire-Pritchett, P 
Schoenfelder, Stefan  ORCID logo  https://orcid.org/0000-0002-3200-8133
Várnai, C 
Wingett, SW 
Cairns, J 

Abstract

Long-range cis-regulatory elements such as enhancers coordinate cell-specific transcriptional programmes by engaging in DNA looping interactions with target promoters. Deciphering the interplay between the promoter connectivity and activity of cis-regulatory elements during lineage commitment is crucial for understanding developmental transcriptional control. Here, we use Promoter Capture Hi-C to generate a high-resolution atlas of chromosomal interactions involving ~22,000 gene promoters in human pluripotent and lineage-committed cells, identifying putative target genes for known and predicted enhancer elements. We reveal extensive dynamics of cis-regulatory contacts upon lineage commitment, including the acquisition and loss of promoter interactions. This spatial rewiring occurs preferentially with predicted changes in the activity of cis-regulatory elements and is associated with changes in target gene expression. Our results provide a global and integrated view of promoter interactome dynamics during lineage commitment of human pluripotent cells.

Description

Keywords

chromosomes, cis-regulatory units, developmental biology, gene regulation, genes, human, human embryonic stem cells, lineage committment, nuclear architecture, promoter capture Hi-C, stem cells

Journal Title

eLife

Conference Name

Journal ISSN

2050-084X
2050-084X

Volume Title

6

Publisher

eLife Sciences Publications Ltd
Sponsorship
Medical Research Council (MC_PC_12009)
Biotechnology and Biological Sciences Research Council (BBS/E/B/000C0405)
Biotechnology and Biological Sciences Research Council (BBS/E/B/000C0404)
Wellcome Trust (WT093736), Biotechnology and Biological Sciences Research Council (BB/J004480/1), Medical Research Council (MR/J003808/1)