Yeast phospholipase C is required for normal glucose metabolism, acetyl‐CoA homeostasis, and global histone acetylation (800.1)

Abstract

Phospholipase C (Plc1p) is required for the initial step of inositol polyphosphates (InsPs) synthesis. Plc1p is also required for normal level of histone acetylation; plc1∆ cells that do not synthesize any InsPs display decreased acetylation of bulk histones, global hypoacetylation of chromatin histones, and altered transcriptional regulation. In accordance with the role of Plc1p in supporting histone acetylation, plc1∆ mutation is synthetically lethal with mutations in several subunits of SAGA and NuA4 histone acetyltransferase (HAT) complexes. Conversely, the growth rate, sensitivity to multiple stresses, and the transcriptional defects of plc1∆ cells are partially suppressed by deletion of histone deacetylase HDA1. The histone hypoacetylation in plc1Δ cells is due to the defect in Grr1p/proteasome‐dependent degradation of repressor Mth1p, and consequently lower expression of the HXT genes and reduced conversion of glucose to acetyl‐CoA, a substrate for HATs. Our current experiments test three possible mechanisms whereby InsPs affect Mth1p degradation: (i) InsPs are required for Mth1p phosphorylation prior to degradation, (ii) InsPs are required for Grr1p activity, and (iii) InsPs are required for the activity of the proteasome.Grant Funding Source: Supported by NIH