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

Research output: Contribution to journalArticle

Authors

  • Paula Freire-Pritchett
  • Stefan Schoenfelder
  • 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

Colleges, School and Institutes

External organisations

  • Nuclear Dynamics Programme, Babraham Institute, Cambridge, UK

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.

Details

Original languageEnglish
Article numbere21926
Number of pages26
JournalElife
Volume6
Publication statusPublished - 23 Mar 2017