title: Condensin I and II Complexes License Full Estrogen Receptor α-Dependent Enhancer Activation.
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.
authors.affiliation: 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.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Yiren
authors.initials: Y
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Soohwan
authors.initials: S
authors.lastname: Oh
authors.affiliation: 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.
authors.forename: Qi
authors.initials: Q
authors.lastname: Ma
authors.affiliation: 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.
authors.forename: Daria
authors.initials: D
authors.lastname: Merkurjev
authors.affiliation: Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Song
authors.affiliation: Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Tanasa
authors.affiliation: School of Basic Medical Sciences, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Xin
authors.initials: X
authors.lastname: He
authors.affiliation: Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Aaron Yun
authors.initials: AY
authors.lastname: Chen
authors.affiliation: Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Kenny
authors.initials: K
authors.lastname: Ohgi
authors.affiliation: Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rosenfeld
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D004958:Estradiol / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D007399:Interphase; D061986:MCF-7 Cells; D008954:Models, Biological; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D000078723:Nuclear Receptor Interacting Protein 1; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000251:Adenosine Triphosphatases; D002843:Chromatin; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D004958:Estradiol; D047628:Estrogen Receptor alpha; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1; D012334:RNA, Neoplasm; D044767:Ubiquitin-Protein Ligases; C506487:ESR1 protein, human; C000627127:NRIP1 protein, human; C108312:condensin complexes; C000588989:HECTD1 protein, human