Lineage-specific dynamic and pre-established enhancer – promoter contacts cooperate in terminal differentiation
Nature Genetics 49, 1522 (2017).
doi:10.1038/ng.3935
Authors: Adam J Rubin, Brook C Barajas, Mayra Furlan-Magaril, Vanessa Lopez-Pajares, Maxwell R Mumbach, Imani Howard, Daniel S Kim, Lisa D Boxer, Jonathan Cairns, Mikhail Spivakov, Steven W Wingett, Minyi Shi, Zhixin Zhao, William J Greenleaf, Anshul Kundaje, Michael Snyder, Howard Y Chang, Peter Fraser & Paul A Khavari
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 ce...
Source: Nature Genetics - Category: Genetics & Stem Cells Authors: Adam J Rubin Brook C Barajas Mayra Furlan-Magaril Vanessa Lopez-Pajares Maxwell R Mumbach Imani Howard Daniel S Kim Lisa D Boxer Jonathan Cairns Mikhail Spivakov Steven W Wingett Minyi Shi Zhixin Zhao William J Greenleaf Anshul Kundaje Michael Snyder Howa Tags: Letter Source Type: research
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