Genome-scale network model of metabolism and histone acetylation reveals metabolic dependencies of histone deacetylase inhibitors.
Genome-scale metabolic modeling
KDAC inhibitors
Metabolic network
Metabolic regulation
Protein acetylation
Protein deacetylases (KDACs)
Journal
Genome biology
ISSN: 1474-760X
Titre abrégé: Genome Biol
Pays: England
ID NLM: 100960660
Informations de publication
Date de publication:
01 03 2019
01 03 2019
Historique:
received:
08
11
2018
accepted:
21
02
2019
entrez:
3
3
2019
pubmed:
3
3
2019
medline:
22
3
2019
Statut:
epublish
Résumé
Histone acetylation plays a central role in gene regulation and is sensitive to the levels of metabolic intermediates. However, predicting the impact of metabolic alterations on acetylation in pathological conditions is a significant challenge. Here, we present a genome-scale network model that predicts the impact of nutritional environment and genetic alterations on histone acetylation. It identifies cell types that are sensitive to histone deacetylase inhibitors based on their metabolic state, and we validate metabolites that alter drug sensitivity. Our model provides a mechanistic framework for predicting how metabolic perturbations contribute to epigenetic changes and sensitivity to deacetylase inhibitors.
Identifiants
pubmed: 30823893
doi: 10.1186/s13059-019-1661-z
pii: 10.1186/s13059-019-1661-z
pmc: PMC6397465
doi:
Substances chimiques
Histone Deacetylase Inhibitors
0
Histones
0
Vorinostat
58IFB293JI
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
49Commentaires et corrections
Type : CommentIn
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