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Phase-separation: a possible new layer for transcriptional regulation by glucocorticoid receptor

Glucocorticoids (GCs) are hormones involved in circadian adaptation and stress response, and it is also noteworthy that these steroidal molecules present potent anti-inflammatory action through GC receptors (GR). Upon ligand-mediated activation, GR translocates to the nucleus, and regulates gene exp...

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Autores principales: Pinheiro, Ester da Silva, Preato, André Maciel, Petrucci, Tamirez Villas Boas, dos Santos, Lucas Souza, Glezer, Isaias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10145926/
https://www.ncbi.nlm.nih.gov/pubmed/37124728
http://dx.doi.org/10.3389/fendo.2023.1160238
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author Pinheiro, Ester da Silva
Preato, André Maciel
Petrucci, Tamirez Villas Boas
dos Santos, Lucas Souza
Glezer, Isaias
author_facet Pinheiro, Ester da Silva
Preato, André Maciel
Petrucci, Tamirez Villas Boas
dos Santos, Lucas Souza
Glezer, Isaias
author_sort Pinheiro, Ester da Silva
collection PubMed
description Glucocorticoids (GCs) are hormones involved in circadian adaptation and stress response, and it is also noteworthy that these steroidal molecules present potent anti-inflammatory action through GC receptors (GR). Upon ligand-mediated activation, GR translocates to the nucleus, and regulates gene expression related to metabolism, acute-phase response and innate immune response. GR field of research has evolved considerably in the last decades, providing varied mechanisms that contributed to the understanding of transcriptional regulation and also impacted drug design for treating inflammatory diseases. Liquid-liquid phase separation (LLPS) in cellular processes represents a recent topic in biology that conceptualizes membraneless organelles and microenvironments that promote, or inhibit, chemical reactions and interactions of protein or nucleic acids. The formation of these molecular condensates has been implicated in gene expression control, and recent evidence shows that GR and other steroid receptors can nucleate phase separation (PS). Here we briefly review the varied mechanisms of transcriptional control by GR, which are largely studied in the context of inflammation, and further present how PS can be involved in the control of gene expression. Lastly, we consider how the reported advances on LLPS during transcription control, specially for steroid hormone receptors, could impact the different modalities of GR action on gene expression, adding a new plausible molecular event in glucocorticoid signal transduction.
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spelling pubmed-101459262023-04-29 Phase-separation: a possible new layer for transcriptional regulation by glucocorticoid receptor Pinheiro, Ester da Silva Preato, André Maciel Petrucci, Tamirez Villas Boas dos Santos, Lucas Souza Glezer, Isaias Front Endocrinol (Lausanne) Endocrinology Glucocorticoids (GCs) are hormones involved in circadian adaptation and stress response, and it is also noteworthy that these steroidal molecules present potent anti-inflammatory action through GC receptors (GR). Upon ligand-mediated activation, GR translocates to the nucleus, and regulates gene expression related to metabolism, acute-phase response and innate immune response. GR field of research has evolved considerably in the last decades, providing varied mechanisms that contributed to the understanding of transcriptional regulation and also impacted drug design for treating inflammatory diseases. Liquid-liquid phase separation (LLPS) in cellular processes represents a recent topic in biology that conceptualizes membraneless organelles and microenvironments that promote, or inhibit, chemical reactions and interactions of protein or nucleic acids. The formation of these molecular condensates has been implicated in gene expression control, and recent evidence shows that GR and other steroid receptors can nucleate phase separation (PS). Here we briefly review the varied mechanisms of transcriptional control by GR, which are largely studied in the context of inflammation, and further present how PS can be involved in the control of gene expression. Lastly, we consider how the reported advances on LLPS during transcription control, specially for steroid hormone receptors, could impact the different modalities of GR action on gene expression, adding a new plausible molecular event in glucocorticoid signal transduction. Frontiers Media S.A. 2023-04-14 /pmc/articles/PMC10145926/ /pubmed/37124728 http://dx.doi.org/10.3389/fendo.2023.1160238 Text en Copyright © 2023 Pinheiro, Preato, Petrucci, dos Santos and Glezer https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Pinheiro, Ester da Silva
Preato, André Maciel
Petrucci, Tamirez Villas Boas
dos Santos, Lucas Souza
Glezer, Isaias
Phase-separation: a possible new layer for transcriptional regulation by glucocorticoid receptor
title Phase-separation: a possible new layer for transcriptional regulation by glucocorticoid receptor
title_full Phase-separation: a possible new layer for transcriptional regulation by glucocorticoid receptor
title_fullStr Phase-separation: a possible new layer for transcriptional regulation by glucocorticoid receptor
title_full_unstemmed Phase-separation: a possible new layer for transcriptional regulation by glucocorticoid receptor
title_short Phase-separation: a possible new layer for transcriptional regulation by glucocorticoid receptor
title_sort phase-separation: a possible new layer for transcriptional regulation by glucocorticoid receptor
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10145926/
https://www.ncbi.nlm.nih.gov/pubmed/37124728
http://dx.doi.org/10.3389/fendo.2023.1160238
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