增强子
生物
雄激素受体
细胞生物学
受体
转录因子
功能(生物学)
细胞
抄写(语言学)
增强子rna
生物物理学
计算生物学
基因
生物化学
遗传学
语言学
哲学
前列腺癌
癌症
作者
Lizhen Chen,Zhao Zhang,Qinyu Han,Barun Kumar Maity,Letícia Rodrigues,Emily Zboril,Rashmi Adhikari,Su Hyuk Ko,Xin Li,Shawn Yoshida,Pengya Xue,Emilie Phillips Smith,Kexin Xu,Qianben Wang,Tim Hui-Ming Huang,Shasha Chong,Zhijie Liu
标识
DOI:10.1016/j.molcel.2023.08.027
摘要
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.
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