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MCB Accepts, published online ahead of print on 29 October 2007
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Mol. Cell. Biol. doi:10.1128/MCB.01307-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The transcriptional adaptor Ada3 of Drosophila is required for histone modification, position effect variegation and transcription

Benjamin Grau, Cristina Popescu, Laura Torroja, Daniel Ortuño-Sahagún, Imre Boros, and Alberto Ferrús*

Dpt. Cellular, Molecular and Developmental Neurobiology, Cajal Institute, C.S.I.C., Ave. Dr. Arce 37, Madrid 28002, Spain; Institute of Biochemistry, Biological Research Center, Temesvári krt. 62, H-6726 Szeged, Hungary; Department of Biochemistry HAS-USZ Chromatin Structure and Gene Expression Research Group, University of Szeged, Közép fasor 52, H-6726 Szeged, Hungary

* To whom correspondence should be addressed. Email: aferrus{at}cajal.csic.es.


   Abstract

The Drosophila gene diskette (dik/dAda3) encodes a protein 29% identical to human ADA3, a subunit of GCN5-containing histone acetyltransferase complexes (HAT). 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 in dGcn5 and dAda2a, but not in dAda2b, mutant backgrounds. In dAda3 mutants, 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 in dAda3 and dGcn5 mutants. Variegation for white (wm4) and scute (Hwv) genes, caused by rearrangements of X chromosome heterochromatin, is modified in a dAda3+ gene dosage dependent manner. The effect is not observed with rearrangements involving Y heterochromatin (bwD), euchromatin (Scutoid), or transvection effects on chromosomal pairing (white/zeste interaction). Activity of scute gene enhancers, targets for Iroquoi transcription factors, is abolished in dAda3 mutants. Also, Iroquoi phenotypes are sensitive to dAda3+ gene dosage. We conclude that dADA3 plays a role in HAT complexes which acetylate H3 and H4 at specific residues. In turn, this results in chromatin structural effects of certain rearrangements, and transcription of specific genes.







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