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

Title: Lineage-specific dynamic and pre-established enhancer-promoter contacts cooperate in terminal differentiation.
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Name(s): Rubin, Adam J, author
Barajas, Brook C, author
Furlan-Magaril, Mayra, author
Lopez-Pajares, Vanessa, author
Mumbach, Maxwell R, author
Howard, Imani, author
Kim, Daniel S, author
Boxer, Lisa D, author
Cairns, Jonathan, author
Spivakov, Mikhail, author
Wingett, Steven W, author
Shi, Minyi, author
Zhao, Zhixin, author
Greenleaf, William J, author
Kundaje, Anshul, author
Snyder, Michael, author
Chang, Howard Y, author
Fraser, Peter, author
Khavari, Paul A, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2017-10-01
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: 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.
Identifier: FSU_pmch_28805829 (IID), 10.1038/ng.3935 (DOI), PMC5715812 (PMCID), 28805829 (RID), 28805829 (EID), ng.3935 (PII)
Grant Number: T32 GM007276, T32 HG000044, R01 AR045192, U01 HG007919, R01 HL122887
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5715812.
Subject(s): Acetylation
Calcium/pharmacology
Cell Differentiation/drug effects
Cell Differentiation/genetics
Cell Lineage/genetics
Cells, Cultured
Chromosomes, Human/genetics
Chromosomes, Human/ultrastructure
Enhancer Elements, Genetic/genetics
Epidermal Cells
Gene Expression Regulation/genetics
Gene Library
Histone Code
Histones/metabolism
Humans
Keratinocytes/cytology
Keratinocytes/metabolism
Male
Promoter Regions, Genetic/genetics
Protein Processing, Post-Translational
RNA/genetics
RNA Interference
Transcription Factors/metabolism
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_28805829
Owner Institution: FSU
Is Part Of: Nature genetics.
1546-1718
Issue: iss. 10, vol. 49

Choose the citation style.
Rubin, A. J., Barajas, B. C., Furlan-Magaril, M., Lopez-Pajares, V., Mumbach, M. R., Howard, I., … Khavari, P. A. (2017). Lineage-specific dynamic and pre-established enhancer-promoter contacts cooperate in terminal differentiation. Nature Genetics. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_28805829