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

eLife

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[1] Department of Genetics and Molecular Medicine, King's College London School of Medicine, London, United Kingdom;Epigenetics Programme, Babraham Institute, Cambridge, United Kingdom;Epigenetics Programme, Babraham Institute, Cambridge, United Kingdom;Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom;Nuclear Dynamics Programme, Babraham Institute, Cambridge, United Kingdom;

关键词: gene regulation;    cis-regulatory units;    human embryonic stem cells;    lineage committment;    nuclear architecture;    promoter capture Hi-C;    Human;   

DOI  :  10.7554/eLife.21926

来源: publisher

【 摘 要 】

10.7554/eLife.21926.001Long-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.DOI: http://dx.doi.org/10.7554/eLife.21926.001

【 授权许可】

CC BY