HNF4A modulates glucocorticoid action in the liver.
CP: Molecular biology
ChIP
HNF4A
chromatin
cistrome
glucocorticoid receptor
liver
mouse
nuclear receptor
tissue specificity
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
19 04 2022
19 04 2022
Historique:
received:
14
04
2021
revised:
24
01
2022
accepted:
29
03
2022
entrez:
20
4
2022
pubmed:
21
4
2022
medline:
23
4
2022
Statut:
ppublish
Résumé
The glucocorticoid receptor (GR) is a nuclear receptor critical to the regulation of energy metabolism and inflammation. The actions of GR are dependent on cell type and context. Here, we demonstrate the role of liver lineage-determining factor hepatocyte nuclear factor 4A (HNF4A) in defining liver specificity of GR action. In mouse liver, the HNF4A motif lies adjacent to the glucocorticoid response element (GRE) at GR binding sites within regions of open chromatin. In the absence of HNF4A, the liver GR cistrome is remodeled, with loss and gain of GR recruitment evident. Loss of chromatin accessibility at HNF4A-marked sites associates with loss of GR binding at weak GRE motifs. GR binding and chromatin accessibility are gained at sites characterized by strong GRE motifs, which show GR recruitment in non-liver tissues. The functional importance of these HNF4A-regulated GR sites is indicated by an altered transcriptional response to glucocorticoid treatment in the Hnf4a-null liver.
Identifiants
pubmed: 35443180
pii: S2211-1247(22)00455-7
doi: 10.1016/j.celrep.2022.110697
pmc: PMC9380254
pii:
doi:
Substances chimiques
Chromatin
0
Glucocorticoids
0
Hepatocyte Nuclear Factor 4
0
Hepatocyte Nuclear Factors
0
Hnf4a protein, mouse
0
Receptors, Glucocorticoid
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
110697Subventions
Organisme : Wellcome Trust
ID : 107849/Z/15/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 107851/Z/15/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P00279X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P023576/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N021479/1
Pays : United Kingdom
Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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