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

• DOI: 10.1016/j.molcel.2015.06.002
• Publication Date: 2015-07-10T03:42:08Z
• Authors: Wenbo Li; Yiren Hu; Soohwan Oh; Qi Ma; Daria Merkurjev; Xiaoyuan Song; Xiang Zhou; Zhijie Liu; Bogdan Tanasa; Xin He; Aaron Yun Chen; Kenny Ohgi; Jie Zhang; Wen Liu; Michael G. Rosenfeld
• Keywords: 0301 basic medicine; Medical and Health Sciences; Models; 2.1 Biological and endogenous factors; Aetiology; Cancer; Adenosine Triphosphatases; Estradiol; Adaptor Proteins; Nuclear Proteins; DNA, Neoplasm; Biological Sciences; Chromatin; Nuclear Receptor Interacting Protein 1; DNA-Binding Proteins; Enhancer Elements, Genetic; Gene Knockdown Techniques; MCF-7 Cells; Female; Protein Binding; Enhancer Elements; 1.1 Normal biological development and functioning; Ubiquitin-Protein Ligases; Molecular Sequence Data; Breast Neoplasms; Models, Biological; Promoter Regions; 03 medical and health sciences; Genetic; Underpinning research; Breast Cancer; Genetics; Humans; Molecular Biology; Interphase; Adaptor Proteins, Signal Transducing; Binding Sites; Base Sequence; Signal Transducing; Ubiquitination; Estrogen Receptor alpha; DNA; Cell Biology; Biological; Estrogen; Multiprotein Complexes; Neoplasm; RNA; Generic health relevance; Developmental Biology

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.