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Metabolic Regulation of Gene Expression by Histone Lysine β-Hydroxybutyrylation
- Source :
- Molecular Cell. 62:194-206
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Here we report the identification and verification of a β-hydroxybutyrate-derived protein modification, lysine β-hydroxybutyrylation (Kbhb), as a new type of histone mark. Histone Kbhb marks are dramatically induced in response to elevated β-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 up-regulated in starvation-responsive metabolic pathways. Histone β-hydroxybutyrylation thus represents a new epigenetic regulatory mark that couples metabolism to gene expression, offering a new avenue to study chromatin regulation and the diverse functions of β-hydroxybutyrate in the context of important human pathophysiological states, including diabetes, epilepsy, and neoplasia.
- Subjects :
- 0301 basic medicine
Hydroxybutyrates
SAP30
Biology
Article
Streptozocin
Diabetic Ketoacidosis
Epigenesis, Genetic
Histones
03 medical and health sciences
Histone methylation
Histone H2A
Animals
Humans
Promoter Regions, Genetic
Molecular Biology
Histone deacetylase 5
Binding Sites
HDAC11
Histone deacetylase 2
Lysine
Fatty Acids
Cell Biology
Chromatin Assembly and Disassembly
HDAC4
Molecular biology
Mice, Inbred C57BL
Disease Models, Animal
Glucose
HEK293 Cells
030104 developmental biology
Gene Expression Regulation
Liver
Starvation
Histone methyltransferase
Energy Metabolism
Protein Processing, Post-Translational
Subjects
Details
- ISSN :
- 10972765
- Volume :
- 62
- Database :
- OpenAIRE
- Journal :
- Molecular Cell
- Accession number :
- edsair.doi.dedup.....ce4d2df3d959b10d008e5ded1008a3f5