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Nat Genet. 2017 Oct;49(10):1522-1528. doi: 10.1038/ng.3935. Epub 2017 Aug 14.

Lineage-specific dynamic and pre-established enhancer-promoter contacts cooperate in terminal differentiation.

Author information

1
Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA.
2
Nuclear Dynamics Programme, Babraham Institute, Cambridge, UK.
3
Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico.
4
Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.
5
Department of Biological Science, Florida State University, Tallahassee, Florida, USA.
6
Veterans Affairs Palo Alto Healthcare System, Palo Alto, California, USA.

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.

PMID:
28805829
PMCID:
PMC5715812
DOI:
10.1038/ng.3935
[Indexed for MEDLINE]
Free PMC Article

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