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

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
DOI: 10.1016/j.molcel.2015.06.002 Publication Date: 2015-07-10T03:42:08Z
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.
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