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| Status |
Public on Mar 23, 2017 |
| Title |
Global rewiring of cis-regulatory units upon lineage commitment of human embryonic stem cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
Lineage commitment is characterised by orchestrated changes in gene expression and chromatin state. Long-range elements such as enhancers coordinate lineage-specific transcriptional programmes by engaging in DNA looping interactions with target promoters. However, the target genes of most long-range elements remain unknown, hindering an integrated understanding of cis-regulatory gene control. Here, we 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 jointly consider promoters and their associated interacting regions as “cis-regulatory units” that potentially integrate and stabilise regulatory inputs from individual elements. We reveal extensive dynamics of cis-regulatory units upon lineage commitment, including the acquisition and loss of promoter interactions, as well as chromatin state changes at preformed interactions. Finally, we show that reconfiguration of cis-regulatory units associates with changes in target gene expression. Our results therefore provide a high-resolution view of promoter interactome dynamics during lineage commitment and provide insights into the mechanisms of developmental transcriptional regulation.
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| Overall design |
Two human ESC CHi-C biological replicates were generated (comprising 1 and 2 technical replicates) and a human ESC Hi-C dataset. Two human NEC CHi-C biological replicates were generated and a human NEC Hi-C dataset. Two RNA-Seq biological replicates for both human ESC and NEC were generated.
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| Contributor(s) |
Freire-Pritchett P, Schoenfelder S, Várnai C, Wingett SW, Cairns J, Collier AJ, Garcia R, Osborne C, Fraser P, Rugg-Gunn PJ, Spivakov M |
| Citation(s) |
28332981 |
| |
| Submission date |
Sep 12, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Steven William Wingett |
| E-mail(s) |
steven.wingett@mrc-lmb.cam.ac.uk
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| Organization name |
MRC Laboratory of Molecular Biology
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| Department |
Cell Biology
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| Street address |
Francis Crick Avenue, Cambridge Biomedical Campus
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| City |
Cambridge |
| State/province |
Cambs |
| ZIP/Postal code |
CB2 0QH |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA342627 |
| SRA |
SRP089694 |
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