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.
Highlights
Cell fate decisions are associated with profound changes in chromatin organisation, which underlie the activation of lineage-specific and the silencing of lineage-inappropriate genes (Buecker and Wysocka, 2012; Bulger and Groudine, 2010; Calo and Wysocka, 2013; Hallikas et al, 2006; Ong and Corces, 2012)
Processed datasets have been made available through Open Science Framework, and raw sequencing reads have been deposited to Gene Expression Omnibus
To investigate the underlying processes that drive changes in cis-regulatory units (CRUs) organisation during cell lineage commitment, we studied the dynamics of promoter interactions and chromatin states at the individual promoter-interacting region (PIR)
Summary
Cell fate decisions are associated with profound changes in chromatin organisation, which underlie the activation of lineage-specific and the silencing of lineage-inappropriate genes (Buecker and Wysocka, 2012; Bulger and Groudine, 2010; Calo and Wysocka, 2013; Hallikas et al, 2006; Ong and Corces, 2012). The definition of chromatin signatures has enabled the genome-wide identification of enhancer elements across multiple human cell types (ENCODE Project Consortium, 2012; Heintzman et al, 2007, 2009; Pennacchio et al, 2006; Rada-Iglesias et al, 2011; Kundaje et al, 2015). Chromatin states can provide a robust readout of cis-regulatory activity associated with poised and active enhancers and have been used to show that widespread changes in enhancer position and activity occur upon cell fate decisions such as the lineage commitment of pluripotent cells (Creyghton et al, 2010; Rada-Iglesias et al, 2011; Zentner et al, 2011)
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