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- Title
Global reorganisation of cis-regulatory units upon lineage commitment of human embryonic stem cells.
- Authors
Freire-Pritchett, Paula; Schoenfelder, Stefan; Vá Rnai, Csilla; Wingett, Steven W.; Cairns, Jonathan; Collier, Amanda J.; García-Vílchez, Raquel; Furlan-Magaril, Mayra; Osborne, Cameron S.; Fraser, Peter; Rugg-Gunn, Peter J.; Spivakov, Mikhail
- 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.
- Subjects
HUMAN embryonic stem cells; CIS-regulatory elements (Genetics); PLURIPOTENT stem cells; GENE expression; CELL determination
- Publication
eLife, 2017, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.21926