Hyperacetylated histone H4 is a source of carbon contributing to lipid synthesis.
Acetylation
Epigenetics
Histone Reservoirs
Lipid Metabolism
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
21 Feb 2024
21 Feb 2024
Historique:
received:
26
06
2023
accepted:
31
01
2024
revised:
12
01
2024
medline:
22
2
2024
pubmed:
22
2
2024
entrez:
22
2
2024
Statut:
aheadofprint
Résumé
Histone modifications commonly integrate environmental cues with cellular metabolic outputs by affecting gene expression. However, chromatin modifications such as acetylation do not always correlate with transcription, pointing towards an alternative role of histone modifications in cellular metabolism. Using an approach that integrates mass spectrometry-based histone modification mapping and metabolomics with stable isotope tracers, we demonstrate that elevated lipids in acetyltransferase-depleted hepatocytes result from carbon atoms derived from deacetylation of hyperacetylated histone H4 flowing towards fatty acids. Consistently, enhanced lipid synthesis in acetyltransferase-depleted hepatocytes is dependent on histone deacetylases and acetyl-CoA synthetase ACSS2, but not on the substrate specificity of the acetyltransferases. Furthermore, we show that during diet-induced lipid synthesis the levels of hyperacetylated histone H4 decrease in hepatocytes and in mouse liver. In addition, overexpression of acetyltransferases can reverse diet-induced lipogenesis by blocking lipid droplet accumulation and maintaining the levels of hyperacetylated histone H4. Overall, these findings highlight hyperacetylated histones as a metabolite reservoir that can directly contribute carbon to lipid synthesis, constituting a novel function of chromatin in cellular metabolism.
Identifiants
pubmed: 38383863
doi: 10.1038/s44318-024-00053-0
pii: 10.1038/s44318-024-00053-0
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : EC | Horizon Europe | Excellent Science | HORIZON EUROPE Marie Sklodowska-Curie Actions (MSCA)
ID : 890750
Organisme : European Proteomics Infrastructure Consortium providing access (EPIC-XS)
ID : 0000424
Organisme : European Proteomics Infrastructure Consortium providing access (EPIC-XS)
ID : 0000463
Organisme : Research and Innovation Foundation (RIF)
ID : EXCELLENCE/0421/0342
Organisme : Research and Innovation Foundation (RIF)
ID : EXCELLENCE/0421/0302
Organisme : Research and Innovation Foundation (RIF)
ID : EXCELLENCE/0421/0152
Informations de copyright
© 2024. The Author(s).
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