@misc{10481/98333,
year = {2024},
month = {11},
url = {https://hdl.handle.net/10481/98333},
abstract = {The glucocorticoid and mineralocorticoid receptors (GR and MR, respectively) have
distinct, yet overlapping physiological and pathophysiological functions. There are indications
that both receptors interact functionally and physically, but the precise role of
this interdependence is poorly understood. Here, we analyzed the impact of GR coexpression
on MR genome-wide
transcriptional responses and chromatin binding upon
activation by aldosterone and glucocorticoids, both physiological ligands of this receptor.
Transcriptional responses of MR in the absence of GR result in fewer regulated genes.
In contrast, coexpression of GR potentiates MR-mediated
transcription, particularly in
response to aldosterone, both in cell lines and in the more physiologically relevant model
of mouse colon organoids. MR chromatin binding is altered by GR coexpression in a
locus-and
ligand-specific
way. Single-molecule
tracking of MR suggests that the presence
of GR contributes to productive binding of MR/aldosterone complexes to chromatin.
Together, our data indicate that coexpression of GR potentiates aldosterone-mediated
MR transcriptional activity, even in the absence of glucocorticoids.},
organization = {Research Program
of the NIH, National Cancer Institute, Center for Cancer Research, by grants PID2019-105339RB-
I00,
PID2020-112768RB-
I00,
and PID2022-138788NB-
I00_
22091
(funded by MCIN/AEI/10.13039/501100011033 and “ERDF A way of making Europe,”
MICINN, Spain)},
organization = {Grant PI21/00952 from Instituto de Salud Carlos III (ISCIII,
Spain), cofunded by the European Union},
organization = {Centro de Investigación Biomédica en
Red de Enfermedades Hepáticas y Digestivas (CIBERehd)},
organization = {PRX18/00498 (funded by Programa Estatal
de Promoción del Talento y su Empleabilidad en I + D + i, Subprograma Estatal de
Movilidad, del Plan Estatal de I + D + I, MICINN, Spain)},
organization = {Spanish DCH Ministry of Science, Education and Universities},
organization = {NIH R35-145313
and NSF 2132922},
publisher = {PNAS},
keywords = {steroid receptors},
keywords = {heteromerization},
keywords = {chromatin binding},
title = {The glucocorticoid receptor potentiates aldosterone-induced transcription by the mineralocorticoid receptor},
doi = {10.1073/pnas.2413737121},
author = {A. Johnson, Thomas and Fettweis, Gregory and Wagh, Kaustubh and Ceacero Heras, Diego and Krishnamurthy, Manan and Sánchez De Medina López-Huertas, Fermín and Martínez Augustín, María Olga and Upadhyaya, Arpita and L. Hager, Gordon and Alvarez de la Rosa, Diego},
}