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Global reorganisation of cis-regulatory units upon lineage commitment of human embryonic stem cells

Freire-Pritchett, P; Schoenfelder, S; Várnai, C; Wingett, SW; Cairns, J; Collier, AJ; García-Vílchez, R; ... Spivakov, M; + view all (2017) Global reorganisation of cis-regulatory units upon lineage commitment of human embryonic stem cells. eLIFE , 6 , Article e21926. 10.7554/eLife.21926. Green open access

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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.

Type: Article
Title: Global reorganisation of cis-regulatory units upon lineage commitment of human embryonic stem cells
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.7554/eLife.21926
Publisher version: https://doi.org/10.7554/eLife.21926.001
Language: English
Additional information: © 2017, Freire-Pritchett et al. This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/).
Keywords: DNA, cis-regulatory elements, Promoter Capture Hi-C, Human embryonic stem cells
URI: https://discovery-pp.ucl.ac.uk/id/eprint/10047223
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