Hormone-induced enhancer assembly requires an optimal level of hormone receptor multivalent interactions.
androgen receptor
condensate formation
condensation
enhancer
hormone-induced enhancer assembly
intrinsically disordered region
multivalent interaction
phase separation
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
05 10 2023
05 10 2023
Historique:
received:
31
10
2022
revised:
11
07
2023
accepted:
29
08
2023
pmc-release:
05
10
2024
medline:
26
10
2023
pubmed:
23
9
2023
entrez:
22
9
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37738977
pii: S1097-2765(23)00690-1
doi: 10.1016/j.molcel.2023.08.027
pmc: PMC10592010
mid: NIHMS1929470
pii:
doi:
Substances chimiques
Transcription Factors
0
Hormones
0
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3438-3456.e12Subventions
Organisme : NIA NIH HHS
ID : R01 AG071591
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016042
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM137009
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG070214
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA217297
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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