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Genome-scale network model of metabolism and histone acetylation reveals metabolic dependencies of histone deacetylase inhibitors.


ABSTRACT: 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.

SUBMITTER: Shen F 

PROVIDER: S-EPMC6397465 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Genome-scale network model of metabolism and histone acetylation reveals metabolic dependencies of histone deacetylase inhibitors.

Shen Fangzhou F   Boccuto Luigi L   Pauly Rini R   Srikanth Sujata S   Chandrasekaran Sriram S  

Genome biology 20190301 1


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,  ...[more]

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