Metabolic Regulation of Gene Expression by Histone Lysine ß-Hydroxybutyrylation.
Mol Cell
; 62(2): 194-206, 2016 04 21.
Article
em En
| MEDLINE
| ID: mdl-27105115
ABSTRACT
Here we report the identification and verification of a ß-hydroxybutyrate-derived protein modification, lysine ß-hydroxybutyrylation (Kbhb), as a new type of histone mark. Histone Kbhb marks are dramatically induced in response to elevated ß-hydroxybutyrate levels in cultured cells and in livers from mice subjected to prolonged fasting or streptozotocin-induced diabetic ketoacidosis. In total, we identified 44 histone Kbhb sites, a figure comparable to the known number of histone acetylation sites. By ChIP-seq and RNA-seq analysis, we demonstrate that histone Kbhb is a mark enriched in active gene promoters and that the increased H3K9bhb levels that occur during starvation are associated with genes upregulated in starvation-responsive metabolic pathways. Histone ß-hydroxybutyrylation thus represents a new epigenetic regulatory mark that couples metabolism to gene expression, offering a new avenue to study chromatin regulation and diverse functions of ß-hydroxybutyrate in the context of important human pathophysiological states, including diabetes, epilepsy, and neoplasia.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Inanição
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Histonas
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Processamento de Proteína Pós-Traducional
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Regulação da Expressão Gênica
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Cetoacidose Diabética
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Metabolismo Energético
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Hidroxibutiratos
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Fígado
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article