ACSS2-coupled KAT2A regulates histone H3 lactylation in gene promoter regions and gene expression

We report EGFR activation induces ERK-mediated S267 phosphorylation of acetyl-CoA synthetase 2 (ACSS2) and its subsequent nuclear translocation and complex formation with lysine acetyltransferase 2A (KAT2A).Consequently, KAT2A acts as a lactyltransferase to lactylate histone H3, leading to expression of Wnt/β-catenin, NFκB, and PD-L1, and brain tumor growth and immune evasion. Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for ACSS2,KAT2A and H3K18la with EGF treatment in GBM cells.