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Mol Cell. 2015 Jul 16;59(2):188-202. doi: 10.1016/j.molcel.2015.06.002. Epub 2015 Jul 9.

Condensin I and II Complexes License Full Estrogen Receptor α-Dependent Enhancer Activation.

Author information

1
Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: wel023@ucsd.edu.
2
Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Biological Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA.
3
Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Bioinformatis and System Biology Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA.
4
Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
5
School of Basic Medical Sciences, Beijing University of Chinese Medicine, Beijing 100029, China.
6
Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: mrosenfeld@ucsd.edu.

Abstract

Enhancers instruct spatio-temporally specific gene expression in a manner tightly linked to higher-order chromatin architecture. Critical chromatin architectural regulators condensin I and condensin II play non-redundant roles controlling mitotic chromosomes. But the chromosomal locations of condensins and their functional roles in interphase are poorly understood. Here we report that both condensin complexes exhibit an unexpected, dramatic estrogen-induced recruitment to estrogen receptor α (ER-α)-bound eRNA(+) active enhancers in interphase breast cancer cells, exhibiting non-canonical interaction with ER-α via its DNA-binding domain (DBD). Condensins positively regulate ligand-dependent enhancer activation at least in part by recruiting an E3 ubiquitin ligase, HECTD1, to modulate the binding of enhancer-associated coactivators/corepressors, including p300 and RIP140, permitting full eRNA transcription, formation of enhancer:promoter looping, and the resultant coding gene activation. Collectively, our results reveal an important, unanticipated transcriptional role of interphase condensins in modulating estrogen-regulated enhancer activation and coding gene transcriptional program.

PMID:
26166704
PMCID:
PMC5770188
DOI:
10.1016/j.molcel.2015.06.002
[Indexed for MEDLINE]
Free PMC Article

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