Host: The Japanese Society of Toxicology
Name : The 51st Annual Meeting of the Japanese Society of Toxicology
Date : July 03, 2024 - July 05, 2024
Most proteins are subjected to various types of post-translational modifications (PTMs) to regulate their functions and subcellular localization. Recently, it was reported that some proteins, including histones, are subjected to exogenous PTMs, such as benzoylation and isonicotinylation, derived from environmental carboxylic acids. We have also attempted to identify these novel exogenous PTMs and investigated their physiological effects. In this symposium, we would like to introduce a novel PTMs sorbylation induced by sorbic acid, a widely used food preservative.
First, we generated an anti-pan-lysine-sorbylation antibody and found that sorbic acid induced histone sorbylation in many cell lines in a dose-dependent manner. LC-MS/MS analysis was performed to identify the sorbylation sites in the core histones. The N-terminus of H2B appears to be the major site; therefore, we generated site-specific antibodies against H2B K5 and K11 sorbylation. Using these antibodies, we found that histone sorbylation is rapidly eliminated in cells, and that HDAC1 and HDAC2, which are zinc ion-dependent lysine deacetylases, can catalyze histone desorbylation in vitro. Intriguingly, lysine deacylases HDAC1 and HDAC2 can also catalyze histone sorbylation using sorbic acid, both in vitro and in cells. In addition, RNA-seq and RT-qPCR analyses revealed that sorbic acid induced expression of genes related to cholesterol synthesis in human hepatocarcinoma HepG2 cells. Moreover, genome-wide histone sorbylation analysis using CUT&Tag revealed that histone sorbylation accumulates in the gene promoter. These findings suggest that sorbic acid induces epigenetic changes in gene expression via histone sorbylation.
