Hat1-Dependent Lysine Acetylation Targets Diverse Cellular Functions

Lysine acetylation has emerged as one of the most important post-translational modifications, regulating different biological processes. However, its regulation by lysine acetyltransferases is still unclear in most cases. Hat1 is a lysine acetyltransferase originally identified based on its ability to acetylate histones. Using an unbiased proteomics approach, we have determined how loss of Hat1 affects the mammalian acetylome. Hat1+/+ and Hat1-/- mouse embryonic fibroblast (MEF) cells lines were grown in both glucose- and galactose-containing media, as Hat1 is required for growth on galactose and Hat1-/- cells exhibit defects in mitochondrial function. Following trypsin digestion of whole cell extracts, acetylated peptides were enriched by acetyllysine affinity purification and acetylated peptides were identified and analyzed by label-free quantitation. Comparison of the acetylome from Hat1+/+ cells grown on galactose and glucose demonstrated that there are large carbon source-dependent changes in the mam...