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

Paula Freire-Pritchett, Stefan Schoenfelder, Csilla Varnai, Steven W Wingett, Jonathan Cairns, Amanda J Collier, Raquel Garcia-Vilchez, Mayra Furlan-Magaril, Cameron S Osborne, Peter Fraser, Peter J Rugg-Gunn, Mikhail Spivakov

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)
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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.
Original languageEnglish
Article numbere21926
Number of pages26
JournaleLife
Volume6
DOIs
Publication statusPublished - 23 Mar 2017

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