Transcriptional Adaptor ADA3 ofDrosophila melanogasterIs Required for Histone Modification, Position Effect Variegation, and Transcription

Abstract

ABSTRACTTheDrosophila melanogastergenediskette(also known asdikordAda3) encodes a protein 29% identical to human ADA3, a subunit of GCN5-containing histone acetyltransferase (HAT) complexes. The fly dADA3 is a major contributor to oogenesis, and it is also required for somatic cell viability. dADA3 localizes to chromosomes, and it is significantly reduced indGcn5anddAda2a, but not indAda2b, mutant backgrounds. IndAda3mutants, acetylation at histone H3 K9 and K14, but not K18, and at histone H4 K12, but not K5, K8, and K16, is significantly reduced. Also, phosphorylation at H3 S10 is reduced indAda3anddGcn5mutants. Variegation forwhite(wm4) andscute(Hwv) genes, caused by rearrangements of X chromosome heterochromatin, is modified in adAda3+gene-dosage-dependent manner. The effect is not observed with rearrangements involving Y heterochromatin (bwD), euchromatin (Scutoid), or transvection effects on chromosomal pairing (whiteandzesteinteraction). Activity ofscutegene enhancers, targets forIroquoitranscription factors, is abolished indAda3mutants. Also,Iroquoi-associated phenotypes are sensitive todAda3+gene dosage. We conclude that dADA3 plays a role in HAT complexes which acetylate H3 and H4 at specific residues. In turn, this acetylation results in chromatin structure effects of certain rearrangements and transcription of specific genes.