Rubin, AJ;
Barajas, BC;
Furlan-Magaril, M;
Lopez-Pajares, V;
Mumbach, MR;
Howard, I;
Kim, DS;
... Khavari, PA; + view all
(2017)
Lineage-specific dynamic and pre-established enhancer–promoter contacts cooperate in terminal differentiation.
[Letter].
Nature Genetics
, 49
(10)
pp. 1522-1528.
10.1038/ng.3935.
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Abstract
Chromosome conformation is an important feature of metazoan gene regulation; however, enhancer–promoter contact remodeling during cellular differentiation remains poorly understood. To address this, genome-wide promoter capture Hi-C (CHi-C) was performed during epidermal differentiation. Two classes of enhancer–promoter contacts associated with differentiation-induced genes were identified. The first class ('gained') increased in contact strength during differentiation in concert with enhancer acquisition of the H3K27ac activation mark. The second class ('stable') were pre-established in undifferentiated cells, with enhancers constitutively marked by H3K27ac. The stable class was associated with the canonical conformation regulator cohesin, whereas the gained class was not, implying distinct mechanisms of contact formation and regulation. Analysis of stable enhancers identified a new, essential role for a constitutively expressed, lineage-restricted ETS-family transcription factor, EHF, in epidermal differentiation. Furthermore, neither class of contacts was observed in pluripotent cells, suggesting that lineage-specific chromatin structure is established in tissue progenitor cells and is further remodeled in terminal differentiation.
| Type: | Article |
|---|---|
| Title: | Lineage-specific dynamic and pre-established enhancer–promoter contacts cooperate in terminal differentiation |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/ng.3935 |
| Publisher version: | http://dx.doi.org/10.1038/ng.3935 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Metazoan, Gene regulation, Cell differentiation, Chromosomes, Genetics, Enhancer elements, Gene expression regulation |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10047597 |
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