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Molecular and Cellular Biology, January 2008, p. 376-385, Vol. 28, No. 1
0270-7306/08/$08.00+0     doi:10.1128/MCB.01307-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Transcriptional Adaptor ADA3 of Drosophila melanogaster Is Required for Histone Modification, Position Effect Variegation, and Transcription{triangledown} ,{dagger}

Benjamin Grau,1,{ddagger} Cristina Popescu,2,{ddagger} Laura Torroja,1,# Daniel Ortuño-Sahagún,1,§ Imre Boros,2,3 and Alberto Ferrús1*

Department of Cellular, Molecular, and Developmental Neurobiology, Cajal Institute, C.S.I.C., Ave. Dr. Arce 37, Madrid 28002, Spain,1 Institute of Biochemistry, Biological Research Center, Temesvári krt. 62, H-6726 Szeged, Hungary,2 Department of Biochemistry HAS-USZ Chromatin Structure and Gene Expression Research Group, University of Szeged, Közép Fasor 52, H-6726 Szeged, Hungary3

Received 20 July 2007/ Returned for modification 25 September 2007/ Accepted 17 October 2007

The Drosophila melanogaster gene diskette (also known as dik or dAda3) 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 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 and zeste interaction). Activity of scute gene enhancers, targets for Iroquoi transcription factors, is abolished in dAda3 mutants. Also, Iroquoi-associated 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 acetylation results in chromatin structure effects of certain rearrangements and transcription of specific genes.


* Corresponding author. Mailing address: Cajal Institute, CSIC, Ave. Dr. Arce 37, 28002 Madrid, Spain. Phone: 34 91 5854739. Fax: 34 91 5854754. E-mail: aferrus{at}cajal.csic.es

{triangledown} Published ahead of print on 29 October 2007.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} These authors have contributed equally to this report.

# Present address: Departamento de Biología, Facultad de Ciencias Biológicas, Universidad Autónoma de Madrid, Madrid, Spain.

§ Present address: Department of Cellular and Molecular Biology, Instituto de Neurobiología, Universidad de Guadalajara, Guadalajara, México.


Molecular and Cellular Biology, January 2008, p. 376-385, Vol. 28, No. 1
0270-7306/08/$08.00+0     doi:10.1128/MCB.01307-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




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