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Glucocorticoid receptor condensates link DNA-dependent receptor dimerization and transcriptional transactivation

View ORCID ProfileFilipp Frank, View ORCID ProfileXu Liu, View ORCID ProfileEric A. Ortlund
doi: https://doi.org/10.1101/2020.11.10.376327
Filipp Frank
1Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
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  • For correspondence: filipp.frank@emory.edu eortlun@emory.edu
Xu Liu
1Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
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Eric A. Ortlund
1Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
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  • For correspondence: filipp.frank@emory.edu eortlun@emory.edu
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Abstract

The glucocorticoid receptor (GR) is a ligand-regulated transcription factor (TF) that controls the tissue- and gene-specific transactivation and transrepression of thousands of target genes. Distinct GR DNA binding sequences with activating or repressive activities have been identified, but how they modulate transcription in opposite ways is not known. We show that GR forms phase-separated condensates that specifically concentrate known co-regulators via their intrinsically disordered regions (IDRs) in vitro. A combination of dynamic, multivalent (between IDRs) and specific, stable interactions (between LxxLL motifs and the GR ligand binding domain) control the degree of recruitment. Importantly, GR DNA-binding directs the selective partitioning of co-regulators within GR condensates such that activating DNAs cause enhanced recruitment of co-activators. Our work shows that condensation controls GR function by modulating co-regulator recruitment and provides a mechanism for the up- and down-regulation of GR target genes controlled by distinct DNA recognition elements.

Competing Interest Statement

The authors have declared no competing interest.

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Posted November 10, 2020.
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Glucocorticoid receptor condensates link DNA-dependent receptor dimerization and transcriptional transactivation
Filipp Frank, Xu Liu, Eric A. Ortlund
bioRxiv 2020.11.10.376327; doi: https://doi.org/10.1101/2020.11.10.376327
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Glucocorticoid receptor condensates link DNA-dependent receptor dimerization and transcriptional transactivation
Filipp Frank, Xu Liu, Eric A. Ortlund
bioRxiv 2020.11.10.376327; doi: https://doi.org/10.1101/2020.11.10.376327

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