Histone propionylation (Hprop)

Histone propionylation is an epigenetic post-translational modification characterized by the addition of a three-carbon propionyl group to lysine residues on histone proteins. This modification is primarily mediated by 'writer' enzymes such as p300/CBP (KAT3A/B) and removed by 'eraser' enzymes including histone deacetylases (HDACs) and certain sirtuins (SIRT1/2). It serves as a mark of transcriptionally active chromatin and is highly sensitive to the cellular concentration of propionyl-CoA, linking cellular metabolic status directly to gene expression regulation (Kebede et al., 2017, Nature Communications). While the modification itself is a biological process and not a protein target, the enzymes that regulate its levels are significant therapeutic targets in oncology and metabolic medicine. Aberrant histone propionylation has been implicated in the progression of various cancers and metabolic syndromes where acyl-CoA metabolism is dysregulated (Sabari et al., 2017, Nature Reviews Molecular Cell Biology). Research indicates that small molecule inhibitors targeting p300 or HDACs can effectively modulate the propionylation landscape to treat disease (Chen et al., 2007, Molecular & Cellular Proteomics).

Other names

Histone lysine propionylationLysine propionylationKprHistone acylations

Drugs modulate histone propionylation levels by inhibiting the enzymatic 'writers' (e.g., p300/CBP) that add propionyl groups or 'erasers' (e.g., HDACs and Sirtuins) that remove them, thereby altering gene expression patterns.