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Widespread reorganisation of pluripotent factor binding and gene regulatory interactions between human pluripotent states.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Chovanec, Peter 
Semprich, Claudia I  ORCID logo  https://orcid.org/0000-0002-2446-9028

Abstract

The transition from naive to primed pluripotency is accompanied by an extensive reorganisation of transcriptional and epigenetic programmes. However, the role of transcriptional enhancers and three-dimensional chromatin organisation in coordinating these developmental programmes remains incompletely understood. Here, we generate a high-resolution atlas of gene regulatory interactions, chromatin profiles and transcription factor occupancy in naive and primed human pluripotent stem cells, and develop a network-graph approach to examine the atlas at multiple spatial scales. We uncover highly connected promoter hubs that change substantially in interaction frequency and in transcriptional co-regulation between pluripotent states. Small hubs frequently merge to form larger networks in primed cells, often linked by newly-formed Polycomb-associated interactions. We identify widespread state-specific differences in enhancer activity and interactivity that correspond with an extensive reconfiguration of OCT4, SOX2 and NANOG binding and target gene expression. These findings provide multilayered insights into the chromatin-based gene regulatory control of human pluripotent states.

Description

Keywords

Chromatin, DNA Methylation, Enhancer Elements, Genetic, Gene Expression Regulation, Humans, Nanog Homeobox Protein, Octamer Transcription Factor-3, Pluripotent Stem Cells, Promoter Regions, Genetic, SOXB1 Transcription Factors, Transcription Factors

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

12

Publisher

Springer Science and Business Media LLC
Sponsorship
Biotechnology and Biological Sciences Research Council (BBS/E/B/000C0405)
Biotechnology and Biological Sciences Research Council (BBS/E/B/000C0404)
Medical Research Council (MR/R015724/1)