TY - JOUR
T1 - Global reorganisation of cis-regulatory units upon lineage commitment of human embryonic stem cells
AU - Freire-Pritchett, Paula
AU - Schoenfelder, Stefan
AU - Varnai, Csilla
AU - Wingett, Steven W
AU - Cairns, Jonathan
AU - Collier, Amanda J
AU - Garcia-Vilchez, Raquel
AU - Furlan-Magaril, Mayra
AU - Osborne, Cameron S
AU - Fraser, Peter
AU - Rugg-Gunn, Peter J
AU - Spivakov, Mikhail
PY - 2017/3/23
Y1 - 2017/3/23
N2 - 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.
AB - 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.
UR - http://dx.doi.org/10.7554/elife.21926
U2 - 10.7554/elife.21926
DO - 10.7554/elife.21926
M3 - Article
SN - 2050-084X
VL - 6
JO - eLife
JF - eLife
M1 - e21926
ER -