Global reorganisation of cis-regulatory units upon lineage commitment of human embryonic stem cells
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.
Global rewiring of cis-regulatory units upon lineage commitment of human embryonic stem cellsPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE76626).
Global rewiring of cis-regulatory units upon lineage commitment of human embryonic stem cellsPublicly available via the Open Science Framework.
A unique chromatin signature uncovers early developmental enhancers in humansPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE24447).
Article and author information
- Peter J Rugg-Gunn
Biotechnology and Biological Sciences Research Council (BB/J004480/1)
- Paula Freire-Pritchett
- Stefan Schoenfelder
- Csilla Várnai
- Steven W Wingett
- Jonathan Cairns
- Mayra Furlan-Magaril
- Peter J Fraser
- Mikhail Spivakov
Medical Research Council (MR/J003808/1)
- Amanda J Collier
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Job Dekker, University of Massachusetts Medical School, United States
- Received: September 28, 2016
- Accepted: March 22, 2017
- Accepted Manuscript published: March 23, 2017 (version 1)
- Version of Record published: April 27, 2017 (version 2)
© 2017, Freire-Pritchett et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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