Work

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

Year: 2017

Type: article

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.

Source: eLife

DOI: 10.7554/elife.21926

Authors: Paula Freire-Pritchett, Stefan Schoenfelder, Csilla Várnai, Steven W Wingett, Jonathan Cairns, Amanda J Collier, Raquel García-Vílchez, Mayra Furlan-Magaril, Cameron S Osborne, Peter Fraser, Peter J Rugg-Gunn, Mikhail Spivakov

Institutions: Babraham Institute, Wellcome/MRC Cambridge Stem Cell Institute, University of Cambridge, Wellcome Trust, King's College London

Language: English

Topic: Genomics and Chromatin Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,500

Funders: Wellcome Trust, Medical Research Council, Biotechnology and Biological Sciences Research Council, Erasmus+

Awards: To study epigenetic mechanisms that create heterogeneity and functional diversity in stem cells, development and between individuals, G1278330175, To study epigenetic mechanisms regulating lineage commitment and cell potency, G1349287539, Signalling to the developing epigenome, Computational systems biology of ageing in haematopoiesis and the immune system, G2537149883, Genomic and epigenomic analysis of ageing in haematopoiesis and the immune system., G2992180400, Epigenetic and Signal Transduction Interactions in Development and Stem Cell Differentiation, Systematic characterisation of epigenomes and transcriptomes during early mouse development, G4399328112, Characterisation of a novel NANOG / KDM4B complex to regulate heterochromatin function and chromosome stability in pluripotent stem cells, G7316932277, G7567962354, G8314006176, Studentship DTG Competition 2011, G8755156122

OpenAlex ID: W2602710346

FWCI: 7.37

Cites: 88

Cited by: 161

Related to: 10