Global reorganisation of cis-regulatory units upon lineage commitment of human embryonic stem cells.
Paula Freire-PritchettStefan SchoenfelderCsilla VárnaiSteven W WingettJonathan CairnsAmanda J CollierRaquel García-VílchezMayra Furlan-MagarilCameron S OsbornePeter FraserPeter J Rugg-GunnMikhail SpivakovPublished in: eLife (2017)
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.
Keyphrases
- transcription factor
- gene expression
- single cell
- dna methylation
- endothelial cells
- cell fate
- genome wide identification
- genome wide
- induced apoptosis
- high resolution
- induced pluripotent stem cells
- embryonic stem cells
- pluripotent stem cells
- copy number
- mesenchymal stem cells
- mass spectrometry
- endoplasmic reticulum stress
- multiple sclerosis
- oxidative stress
- heat shock
- signaling pathway
- resting state
- circulating tumor cells
- heat shock protein