Oscillatory cAMP signaling rapidly alters H3K4 methylation.
Animals
Cells, Cultured
Cyclic AMP
/ analogs & derivatives
Demethylation
/ drug effects
Ferrous Compounds
/ metabolism
Gene Silencing
Histones
/ metabolism
Jumonji Domain-Containing Histone Demethylases
/ genetics
Ligands
Methylation
/ drug effects
Oxidoreductases, N-Demethylating
/ genetics
Protein Processing, Post-Translational
/ drug effects
Rats
Receptors, G-Protein-Coupled
/ metabolism
Schwann Cells
Signal Transduction
/ drug effects
Thionucleotides
/ metabolism
Transfection
Journal
Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
12
11
2019
revised:
13
12
2019
accepted:
16
12
2019
entrez:
29
12
2019
pubmed:
29
12
2019
medline:
12
1
2021
Statut:
epublish
Résumé
Epigenetic variation reflects the impact of a dynamic environment on chromatin. However, it remains elusive how environmental factors influence epigenetic events. Here, we show that G protein-coupled receptors (GPCRs) alter H3K4 methylation via oscillatory intracellular cAMP. Activation of Gs-coupled receptors caused a rapid decrease of H3K4me3 by elevating cAMP, whereas stimulation of Gi-coupled receptors increased H3K4me3 by diminishing cAMP. H3K4me3 gradually recovered towards baseline levels after the removal of GPCR ligands, indicating that H3K4me3 oscillates in tandem with GPCR activation. cAMP increased intracellular labile Fe(II), the cofactor for histone demethylases, through a non-canonical cAMP target-Rap guanine nucleotide exchange factor-2 (RapGEF2), which subsequently enhanced endosome acidification and Fe(II) release from the endosome via vacuolar H
Identifiants
pubmed: 31882444
pii: 3/1/e201900529
doi: 10.26508/lsa.201900529
pmc: PMC6935296
pii:
doi:
Substances chimiques
Ferrous Compounds
0
Histones
0
Ligands
0
Receptors, G-Protein-Coupled
0
Thionucleotides
0
histone H3 trimethyl Lys4
0
8-((4-chlorophenyl)thio)cyclic-3',5'-AMP
41941-66-6
Cyclic AMP
E0399OZS9N
Jumonji Domain-Containing Histone Demethylases
EC 1.14.11.-
Kdm5c protein, rat
EC 1.5.-
Oxidoreductases, N-Demethylating
EC 1.5.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NINDS NIH HHS
ID : R01 NS089525
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM066698
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM064337
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM079465
Pays : United States
Informations de copyright
© 2019 Huff et al.
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