Hormone-induced enhancer assembly requires an optimal level of hormone receptor multivalent interactions

Lizhen Chen, Zhao Zhang, Qinyu Han, Barun K. Maity, Leticia Rodrigues, Emily Zboril, Rashmi Adhikari, Su Hyuk Ko, Xin Li, Shawn R. Yoshida, Pengya Xue, Emilie Smith, Kexin Xu, Qianben Wang, Tim Hui Ming Huang, Shasha Chong, Zhijie Liu

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Transcription factors (TFs) activate enhancers to drive cell-specific gene programs in response to signals, but our understanding of enhancer assembly during signaling events is incomplete. Here, we show that androgen receptor (AR) forms condensates through multivalent interactions mediated by its N-terminal intrinsically disordered region (IDR) to orchestrate enhancer assembly in response to androgen signaling. AR IDR can be substituted by IDRs from selective proteins for AR condensation capacity and its function on enhancers. Expansion of the poly(Q) track within AR IDR results in a higher AR condensation propensity as measured by multiple methods, including live-cell single-molecule microscopy. Either weakening or strengthening AR condensation propensity impairs its heterotypic multivalent interactions with other enhancer components and diminishes its transcriptional activity. Our work reveals the requirement of an optimal level of AR condensation in mediating enhancer assembly and suggests that alteration of the fine-tuned multivalent IDR-IDR interactions might underlie AR-related human pathologies.

Original languageEnglish (US)
Pages (from-to)3438-3456.e12
JournalMolecular Cell
Volume83
Issue number19
DOIs
StatePublished - Oct 5 2023

Keywords

  • androgen receptor
  • condensate formation
  • condensation
  • enhancer
  • hormone-induced enhancer assembly
  • intrinsically disordered region
  • multivalent interaction
  • phase separation

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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