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
AUTHORS (15)
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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CITATIONS (104)
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