Interphase condensins regulate ligand-depedent enhancer activation (ChIP-seq)

An emerging theme of gene regulation is the involvement of architectural chromosomal molecules in transcription control. Condensins are critical regulators of mitotic chromosomes, but their interphase chromatin localization and functions remain poorly understood. Here we report that both the condensin I and condensin II complexes exhibit an unexpected, dramatic 17-ß-estradiol-induced preferential recruitment to oestrogen receptor a (ER-a)-bound active enhancers in interphase breast cancer cells, exhibiting non-canonical interaction with ER-a distinct from classic cofactors. Condensins prove to positively regulate ligand-dependent gene and eRNA transcription by modulating a binding equilibrium of enhancer-associated coactivators/corepressors, including p300 and RIP140. This activity was achieved by the condensin-dependent recruitment of an E3 ubiquitin ligase, HECTD1, to active enhancers, where it polyubiquitinates and dismisses corepressor RIP140 to stimulate eRNA transcription. Collectively, our results reveal an important, unanticipated transcriptional role of interphase condensins in modulating enhancer activation, providing new insights into enhancer function in the regulated transcriptional programs Overall design: The ChIP-seqs in this study measure the binding landscapes of condensin subunits, master transcription regulator of estrogen signaling - ERa, histone marks including H3K27ac and transcription coactivators such as p300 in MCF7 cells. The details of each dataset was indicated in each file.