Function and mechanism of histone β-hydroxybutyrylation in health and disease

Abstract

Histone post-translational modifications (HPTMs) are essential epigenetic mechanisms that affect chromatin-associated nuclear processes without altering the DNA sequence. With the application of mass spectrometry-based proteomics, novel histone lysine acylation, such as propionylation, butyrylation, crotonylation, malonylation, succinylation, glutarylation, and lactoylation have been successively discovered. The emerging diversity of the lysine acylation landscape prompted us to investigate the function and mechanism of these novel HPTMs in health and disease. Recently, it has been reported that β-hydroxybutyrate (BHB), the main component of the ketone body, has various protective roles beyond alternative fuel provision during starvation. Histone lysine β-hydroxybutyrylation (Kbhb) is a novel HPTMs identified by mass spectrometry, which regulates gene transcription in response to carbohydrate restriction or elevated BHB levels in vivo and vitro. Recent studies have shown that histone Kbhb is strongly associated with the pathogenesis of metabolic cardiovascular diseases, kidney diseases, tumors, neuropsychiatric disorders, and metabolic diseases suggesting it has different functions from histone acetylation and methylation. This review focuses on the writers, erasers, sites, and underlying functions of histone Kbhb, providing a glimpse into their complex regulation mechanism.

Modulation of beta-hydroxybutyrate in traumatic brain injury

“…These clarify how BHB regulates gene expression, especially in relation to pathways that respond to oxidative stress. The effects of OHB boosted the expression of FOXO3A, catalase, and mitochondrial superoxide dismutase [24 ▪▪ ].…”

Orthogonal Translation for Site-Specific Installation of Post-translational Modifications

“…Lysine β-hydroxybutyrylation is a newly identified PTM in histones and nonhistone proteins in eukaryotes, which links cellular metabolism to gene expression . Emerging evidence shows its association with metabolic diseases, cardiovascular diseases, diabetes, neuropsychiatric disorders, and cancers. , A recent study showed that lysine β-hydroxybutyrylation could improve stability of COVID-19 antibodies in cells . The OTS for genetic encoding of lysine β-hydroxybutyrylation into proteins has been established in both E. coli and mammalian cells with an Mb PylRS variant (C313 V and Y349F) …”

Epigenetic regulation in metabolic diseases: mechanisms and advances in clinical study

“…103 Kbhb is catalysed by p300, while SIRT1 to SIRT3 and HDAC1 to HDAC3 remove Kbhb. 104 In addition, p300 could catalyze lysine propionylation (Kpr), butyrylation (Kbu), crotonylation (Kcr) in histones. 105,106 Histone lysine lactylation (Kla) is a novel histone mark which was first reported in 2019.…”