Global reorganisation ofcis-regulatory units upon lineage commitment of human embryonic stem cells.
Long-rangecis-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 ofcis-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 ofcis-regulatory contacts upon lineage commitment, including the acquisition and loss of promoter interactions. This spatial rewiring occurs preferentially with predicted changes in the activity ofcis-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.
Nuclear Dynamics Programme, Babraham Institute, Cambridge, United Kingdom.
Paula
P
Freire-Pritchett
Nuclear Dynamics Programme, Babraham Institute, Cambridge, United Kingdom.
Stefan
S
Schoenfelder
Nuclear Dynamics Programme, Babraham Institute, Cambridge, United Kingdom.
Csilla
C
Várnai
Nuclear Dynamics Programme, Babraham Institute, Cambridge, United Kingdom.
Steven W
SW
Wingett
Nuclear Dynamics Programme, Babraham Institute, Cambridge, United Kingdom.
Jonathan
J
Cairns
Epigenetics Programme, Babraham Institute, Cambridge, United Kingdom.|Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.
Amanda J
AJ
Collier
Epigenetics Programme, Babraham Institute, Cambridge, United Kingdom.
Raquel
R
García-Vílchez
Nuclear Dynamics Programme, Babraham Institute, Cambridge, United Kingdom.
Mayra
M
Furlan-Magaril
Department of Genetics and Molecular Medicine, King's College London School of Medicine, London, United Kingdom.
Cameron S
CS
Osborne
Nuclear Dynamics Programme, Babraham Institute, Cambridge, United Kingdom.
Peter
P
Fraser
Epigenetics Programme, Babraham Institute, Cambridge, United Kingdom.|Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.
Peter J
PJ
Rugg-Gunn
Nuclear Dynamics Programme, Babraham Institute, Cambridge, United Kingdom.
Mikhail
http://orcid.org/0000-0002-0383-3943
M
Spivakov
D002454:Cell Differentiation; D005786:Gene Expression Regulation; D000066449:Human Embryonic Stem Cells / Q000502:physiology*; D006801:Humans; D011401:Promoter Regions, Genetic; D050436:Regulatory Elements, Transcriptional; D014158:Transcription, Genetic
chromosomes; cis-regulatory units; developmental biology; gene regulation; genes; human; human embryonic stem cells; lineage committment; nuclear architecture; promoter capture Hi-C; stem cells