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PMID: 17967867 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Transcriptional adaptor ADA3 of Drosophila melanogaster is required for histone modification, position effect variegation, and transcription.

Molecular and cellular biology ·Vol. 28 ·No. 1 ·2008-01-00 ·Pages 376-85

Grau B, Popescu C, Torroja L, Ortuño-Sahagún D, Boros I, Ferrús A

Abstract

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 (w(m4)) and scute (Hw(v)) 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 (bw(D)), 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.

MeSH Terms
Acetylation Adaptor Proteins, Signal Transducing/genetics,metabolism Animals Drosophila Proteins/classification,genetics,metabolism Drosophila melanogaster/genetics,metabolism Gene Expression Regulation Histone Acetyltransferases/classification,genetics,metabolism Histones/metabolism Mutation/genetics Phenotype Phosphorylation Transcription, Genetic/genetics X Chromosome/genetics
Chemicals
Adaptor Proteins, Signal Transducing Drosophila Proteins Histones ADA3 protein, Drosophila Histone Acetyltransferases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Grau Benjamin
Department of Cellular, Molecular, and Developmental Neurobiology, Cajal Institute, CSIC, Ave. Dr. Arce 37, 28002 Madrid, Spain.
Popescu Cristina
Torroja Laura
Ortuño-Sahagún Daniel
Boros Imre
Ferrús Alberto
References (66)
66 references, click to expand
  1. A Drosophila protein that imparts directionality on a chromatin insulator is an enhancer of position-effect variegation.
    Cell. 1995 Aug 25;82(4):587-97 PMID: 7664338
  2. Histone acetylation and transcriptional regulatory mechanisms.
    Genes Dev. 1998 Mar 1;12(5):599-606 PMID: 9499396
  3. The Iroquois homeodomain proteins are required to specify body wall identity in Drosophila.
    Genes Dev. 1999 Jul 1;13(13):1754-61 PMID: 10398687
  4. ADA3: a gene, identified by resistance to GAL4-VP16, with properties similar to and different from those of ADA2.
    Mol Cell Biol. 1993 Oct;13(10):5981-9 PMID: 8413201
  5. Snf1--a histone kinase that works in concert with the histone acetyltransferase Gcn5 to regulate transcription.
    Science. 2001 Aug 10;293(5532):1142-6 PMID: 11498592
  6. Cloning of Drosophila GCN5: conserved features among metazoan GCN5 family members.
    Nucleic Acids Res. 1998 Jun 15;26(12):2948-54 PMID: 9611240
  7. Cooperation between complexes that regulate chromatin structure and transcription.
    Cell. 2002 Feb 22;108(4):475-87 PMID: 11909519
  8. Histone-like TAFs within the PCAF histone acetylase complex.
    Cell. 1998 Jul 10;94(1):35-44 PMID: 9674425
  9. Human papilloma virus 16 E6 oncoprotein inhibits retinoic X receptor-mediated transactivation by targeting human ADA3 coactivator.
    J Biol Chem. 2002 Nov 22;277(47):45611-8 PMID: 12235159
  10. Chromatin structure and dynamics: functional implications.
    Biochimie. 2001 Nov-Dec;83(11-12):1029-39 PMID: 11879731
  11. The homologous Drosophila transcriptional adaptors ADA2a and ADA2b are both required for normal development but have different functions.
    Mol Cell Biol. 2005 Sep;25(18):8215-27 PMID: 16135810
  12. The haplolethal region at the 16F gene cluster of Drosophila melanogaster: structure and function.
    Genetics. 1999 Jan;151(1):163-75 PMID: 9872957
  13. Nuclear organization and gene expression: homologous pairing and long-range interactions.
    Curr Opin Cell Biol. 1997 Jun;9(3):388-95 PMID: 9159074
  14. Localizing transcription factors on chromatin by immunofluorescence.
    Methods. 2002 Jan;26(1):3-9 PMID: 12054899
  15. Cross-regulatory interactions between the proneural achaete and scute genes of Drosophila.
    Science. 1991 Mar 22;251(5000):1485-7 PMID: 1900954
  16. Recruitment of HAT complexes by direct activator interactions with the ATM-related Tra1 subunit.
    Science. 2001 Jun 22;292(5525):2333-7 PMID: 11423663
  17. ADA3, a putative transcriptional adaptor, consists of two separable domains and interacts with ADA2 and GCN5 in a trimeric complex.
    Mol Cell Biol. 1995 Mar;15(3):1203-9 PMID: 7862114
  18. Histone acetyltransferase complexes: one size doesn't fit all.
    Nat Rev Mol Cell Biol. 2007 Apr;8(4):284-95 PMID: 17380162
  19. Different contributions of pannier and wingless to the patterning of the dorsal mesothorax of Drosophila.
    Development. 1999 Aug;126(16):3523-32 PMID: 10409499
  20. Histone acetyltransferase activity and interaction with ADA2 are critical for GCN5 function in vivo.
    EMBO J. 1997 Feb 3;16(3):555-65 PMID: 9034338
  21. Reduction of transcription by homologue asynapsis in Drosophila imaginal discs.
    Nature. 1996 Jun 27;381(6585):807-10 PMID: 8657287
  22. Gene activation by histone and factor acetyltransferases.
    Curr Opin Cell Biol. 1999 Jun;11(3):336-41 PMID: 10395565
  23. White as a reporter gene to detect transcriptional silencers specifying position-specific gene expression during Drosophila melanogaster eye development.
    Genetics. 1995 Nov;141(3):1075-86 PMID: 8582614
  24. Molecular genetics of the achaete-scute gene complex of D. melanogaster.
    Cell. 1985 Feb;40(2):327-38 PMID: 3917860
  25. Genetic analysis of the Shaker gene complex of Drosophila melanogaster.
    Genetics. 1990 Jun;125(2):383-98 PMID: 2116353
  26. Phosphorylation of histone H3: a balancing act between chromosome condensation and transcriptional activation.
    Trends Genet. 2004 Apr;20(4):214-20 PMID: 15041176
  27. JIL-1, a chromosomal kinase implicated in regulation of chromatin structure, associates with the male specific lethal (MSL) dosage compensation complex.
    J Cell Biol. 2000 May 29;149(5):1005-10 PMID: 10831604
  28. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum.
    Anal Biochem. 1984 Feb;137(1):266-7 PMID: 6329026
  29. The Swi/Snf family nucleosome-remodeling complexes and transcriptional control.
    Trends Genet. 2000 Aug;16(8):345-51 PMID: 10904263
  30. Alteration of nucleosome structure as a mechanism of transcriptional regulation.
    Annu Rev Biochem. 1998;67:545-79 PMID: 9759497
  31. Role of the Ada2 and Ada3 transcriptional coactivators in histone acetylation.
    J Biol Chem. 2002 Mar 8;277(10):7989-95 PMID: 11773077
  32. The Drosophila histone acetyltransferase Gcn5 and transcriptional adaptor Ada2a are involved in nucleosomal histone H4 acetylation.
    Mol Cell Biol. 2006 Dec;26(24):9413-23 PMID: 17030603
  33. Vectors for P-mediated transformation in Drosophila.
    Biotechnology. 1988;10:437-56 PMID: 2850048
  34. Molecular organization of the maternal effect region of the Shaker complex of Drosophila: characterization of an I(A) channel transcript with homology to vertebrate Na channel.
    EMBO J. 1987 Nov;6(11):3419-29 PMID: 16453805
  35. Ectopic gene expression in Drosophila using GAL4 system.
    Methods. 1998 Apr;14(4):367-79 PMID: 9608508
  36. The histone deacetylase RPD3 counteracts genomic silencing in Drosophila and yeast.
    Nature. 1996 Dec 12;384(6609):589-91 PMID: 8955276
  37. Distinct GCN5/PCAF-containing complexes function as co-activators and are involved in transcription factor and global histone acetylation.
    Oncogene. 2007 Aug 13;26(37):5341-57 PMID: 17694077
  38. Comparative analysis of position-effect variegation mutations in Drosophila melanogaster delineates the targets of modifiers.
    Genetics. 1998 Feb;148(2):733-41 PMID: 9504920
  39. Self-association of the Drosophila zeste protein is responsible for transvection effects.
    EMBO J. 1990 Sep;9(9):2959-67 PMID: 2118108
  40. Competition between different variegating rearrangements for limited heterochromatic factors in Drosophila melanogaster.
    Genetics. 1997 Apr;145(4):945-59 PMID: 9093849
  41. Drosophila Med6 is required for elevated expression of a large but distinct set of developmentally regulated genes.
    Mol Cell Biol. 2001 Aug;21(15):5242-55 PMID: 11438678
  42. ADA3-containing complexes associate with estrogen receptor alpha.
    Nucleic Acids Res. 2002 Jun 1;30(11):2508-14 PMID: 12034840
  43. Role of histone modification in chromatin dynamics.
    J Biochem. 2007 May;141(5):609-14 PMID: 17405795
  44. New advances in Drosophila provide opportunities to study gene functions.
    Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9716-7 PMID: 9707540
  45. The SAGA continues: expanding the cellular role of a transcriptional co-activator complex.
    Oncogene. 2007 Aug 13;26(37):5329-40 PMID: 17694076
  46. Human papillomavirus oncoprotein E6 inactivates the transcriptional coactivator human ADA3.
    Mol Cell Biol. 2002 Aug;22(16):5801-12 PMID: 12138191
  47. Pairing-dependent mislocalization of a Drosophila brown gene reporter to a heterochromatic environment.
    Genetics. 1999 Jun;152(2):595-604 PMID: 10353902
  48. Host cell factor and an uncharacterized SANT domain protein are stable components of ATAC, a novel dAda2A/dGcn5-containing histone acetyltransferase complex in Drosophila.
    Mol Cell Biol. 2006 Feb;26(3):871-82 PMID: 16428443
  49. Changes in chromosomal localization of heterochromatin-binding proteins during the cell cycle in Drosophila.
    J Cell Biol. 1998 Mar 23;140(6):1297-306 PMID: 9508764
  50. Tissue-specific transcriptional enhancers may act in trans on the gene located in the homologous chromosome: the molecular basis of transvection in Drosophila.
    EMBO J. 1990 Jul;9(7):2247-56 PMID: 2162766
  51. Synergistic coupling of histone H3 phosphorylation and acetylation in response to epidermal growth factor stimulation.
    Mol Cell. 2000 Jun;5(6):905-15 PMID: 10911985
  52. The language of covalent histone modifications.
    Nature. 2000 Jan 6;403(6765):41-5 PMID: 10638745
  53. The molecular analyses of an antimorphic mutation of Drosophila melanogaster, Scutoid.
    Genetics. 1988 Jul;119(3):647-61 PMID: 16052738
  54. Two Drosophila Ada2 homologues function in different multiprotein complexes.
    Mol Cell Biol. 2003 May;23(9):3305-19 PMID: 12697829
  55. Genetic modification of heterochromatic association and nuclear organization in Drosophila.
    Nature. 1996 Jun 6;381(6582):529-31 PMID: 8632827
  56. The essential gene wda encodes a WD40 repeat subunit of Drosophila SAGA required for histone H3 acetylation.
    Mol Cell Biol. 2006 Oct;26(19):7178-89 PMID: 16980620
  57. Adenovirus E1A requires the yeast SAGA histone acetyltransferase complex and associates with SAGA components Gcn5 and Tra1.
    Oncogene. 2002 Feb 21;21(9):1411-22 PMID: 11857084
  58. Araucan and caupolican, two members of the novel iroquois complex, encode homeoproteins that control proneural and vein-forming genes.
    Cell. 1996 Apr 5;85(1):95-105 PMID: 8620542
  59. A subset of TAF(II)s are integral components of the SAGA complex required for nucleosome acetylation and transcriptional stimulation.
    Cell. 1998 Jul 10;94(1):45-53 PMID: 9674426
  60. The complex language of chromatin regulation during transcription.
    Nature. 2007 May 24;447(7143):407-12 PMID: 17522673
  61. Evidence that two mutations, wDZL and z1, affecting synapsis-dependent genetic behavior of white are transcriptional regulatory mutations.
    Cell. 1985 Apr;40(4):819-25 PMID: 2580637
  62. Structural and functional analysis of yeast putative adaptors. Evidence for an adaptor complex in vivo.
    J Biol Chem. 1996 Mar 1;271(9):5237-45 PMID: 8617808
  63. Phosphorylation of serine 10 in histone H3 is functionally linked in vitro and in vivo to Gcn5-mediated acetylation at lysine 14.
    Mol Cell. 2000 Jun;5(6):917-26 PMID: 10911986
  64. Separate regulatory elements are responsible for the complex pattern of tissue-specific and developmental transcription of the yellow locus in Drosophila melanogaster.
    Genes Dev. 1987 Nov;1(9):996-1004 PMID: 3123324
  65. Developmental regulation of eukaryotic gene loci: which cis-regulatory information is required?
    Trends Genet. 2000 Jul;16(7):310-5 PMID: 10858661
  66. The TAFs in the HAT.
    Cell. 1998 Jul 10;94(1):1-4 PMID: 9674419
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
1098-5549
Published
2008-01-00
Epub
2007-00-29
Pages
376-85
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC2223303
Subset
IM
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