Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

Metabolic regulation of gene expression by histone lysine beta-hydroxybutyrylation.

Xie Z., Zhang D., Chung D., Tang Z., Huang H., Dai L., Qi S., Li J., Colak G., Chen Y., Xia C., Peng C., Ruan H., Kirkey M., Wang D., Jensen L.M., Kwon O.K., Lee S., Pletcher S.D., Tan M., Lombard D.B., White K.P., Zhao H., Li J., Roeder R.G., Yang X., Zhao Y.

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 upregulated 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 diverse functions of β-hydroxybutyrate in the context of important human pathophysiological states, including diabetes, epilepsy, and neoplasia.

Mol. Cell 62:194-206(2016) [PubMed] [Europe PMC]

UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again