Metabolic Regulation of Gene Expression by Histone Lysine β-hydroxybutyrylation
By Zhongyu Xie, Di Zhang, Dongjun Chung, Zhanyun Tang, He Huang, Lunzhi Dai, Shankang Qi, Jingya Li, Gozde Colak, Yue Chen and 17 more. Molecules and Cells, 2016
598 citations recorded by the source corpus.
SUMMARY 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.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/6eec25ce9c78a865b11fdb2dace701836966a4f0
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Citations in the corpus
- Metabolic reprogramming and epigenetic modifications on the path to cancer (2021, methodology): “…showed that with the increase in histone Kbhb modification, the expression of some genes related to physiological responses to fasting was upregulated, such as amino acid catabolism, redox balance, circadian rhythm, and PPAR (peroxisome proliferator-activated receptor) signaling (Xie et al., 2016).”
- Multi-dimensional roles of ketone bodies in fuel metabolism, signaling, and therapeutics (2017, background): “Independently, bOHB directly modifies histone lysine residues (Xie et al., 2016).”
- Cistrome Data Browser: expanded datasets and new tools for gene regulatory analysis (2018, background): “Examples of new factors include ZBTB48 (35,36) and ZMYM3 (37) in human, and SPEN and TERF2IP (38) in mouse; and examples of new histone modifications / variants include H3F3A (37) and H2AFZ (37) in human, and H3K9BHB (39) and H2BK5me1 (40) in mouse (Figure 2D).”