Depletion of histone deacetylase 3 antagonizes PI3K-mediated tissue overgrowth through the acetylation of histone H4 at lysine 16. Drosophila melanogaster

Histone acetylation is one of the best studied gene modifications and has been shown to be involved in numerous important biological processes. Herein，we demonstrate that Hdac3 regulates both organ and body size through the deacetylation of histone H4 at lysine 16 (H4K16ac). H4K16ac is affected by PI3K signaling cascades. Increasing H4K16ac by the depletion of Hdac3 counteracts PI3K-induced tissue overgrowth and PI3K-mediated alterations in the transcription profile. Using microarry, we compared the transcriptional profile between flies over-expressing PI3K and flies co-expressing PI3K and Hdac3 dsRNA. The findings provide further insight into the mechanism of PI3K-mediated growth and chromatin remodeling. Overall design: Total RNA was isolated from Drosophila wing imaginal discs using Trizol reagent and hybridized on Affymetrix microarrays. We performed microarray gene expression profiling from drosophila 3rd wing disc of en-Gal4, PI3K overexpression, HDAC3 RNAi, and PI3K overexpression + Hdac3 RNAi.