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. 1997 Apr 15;16(8):2054–2060. doi: 10.1093/emboj/16.8.2054

mof, a putative acetyl transferase gene related to the Tip60 and MOZ human genes and to the SAS genes of yeast, is required for dosage compensation in Drosophila.

A Hilfiker 1, D Hilfiker-Kleiner 1, A Pannuti 1, J C Lucchesi 1
PMCID: PMC1169808  PMID: 9155031

Abstract

Dosage compensation is a regulatory process that insures that males and females have equal amounts of X-chromosome gene products. In Drosophila, this is achieved by a 2-fold enhancement of X-linked gene transcription in males, relative to females. The enhancement of transcription is mediated by the activity of a group of regulatory genes characterized by the male-specific lethality of their loss-of-function alleles. The products of these genes form a complex that is preferentially associated with numerous sites on the X chromosome in somatic cells of males but not of females. Binding of the dosage compensation complex is correlated with a significant increase in the presence of a specific histone isoform, histone 4 acetylated at Lys16, on this chromosome. Experimental results and sequence analysis suggest that an additional gene, males-absent on the first (mof), encodes a putative acetyl transferase that plays a direct role in the specific histone acetylation associated with dosage compensation. The predicted amino acid sequence of MOF exhibits a significant level of similarity to several other proteins, including the human HIV-1 Tat interactive protein Tip60, the human monocytic leukemia zinc finger protein MOZ and the yeast silencing proteins SAS3 and SAS2.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  2. Baker B. S., Gorman M., Marín I. Dosage compensation in Drosophila. Annu Rev Genet. 1994;28:491–521. doi: 10.1146/annurev.ge.28.120194.002423. [DOI] [PubMed] [Google Scholar]
  3. Bellini M., Lacroix J. C., Gall J. G. A putative zinc-binding protein on lampbrush chromosome loops. EMBO J. 1993 Jan;12(1):107–114. doi: 10.1002/j.1460-2075.1993.tb05636.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Belote J. M., Lucchesi J. C. Control of X chromosome transcription by the maleless gene in Drosophila. Nature. 1980 Jun 19;285(5766):573–575. doi: 10.1038/285573a0. [DOI] [PubMed] [Google Scholar]
  5. Bone J. R., Kuroda M. I. Dosage compensation regulatory proteins and the evolution of sex chromosomes in Drosophila. Genetics. 1996 Oct;144(2):705–713. doi: 10.1093/genetics/144.2.705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bone J. R., Lavender J., Richman R., Palmer M. J., Turner B. M., Kuroda M. I. Acetylated histone H4 on the male X chromosome is associated with dosage compensation in Drosophila. Genes Dev. 1994 Jan;8(1):96–104. doi: 10.1101/gad.8.1.96. [DOI] [PubMed] [Google Scholar]
  7. Brownell J. E., Zhou J., Ranalli T., Kobayashi R., Edmondson D. G., Roth S. Y., Allis C. D. Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell. 1996 Mar 22;84(6):843–851. doi: 10.1016/s0092-8674(00)81063-6. [DOI] [PubMed] [Google Scholar]
  8. Coon S. L., Roseboom P. H., Baler R., Weller J. L., Namboodiri M. A., Koonin E. V., Klein D. C. Pineal serotonin N-acetyltransferase: expression cloning and molecular analysis. Science. 1995 Dec 8;270(5242):1681–1683. doi: 10.1126/science.270.5242.1681. [DOI] [PubMed] [Google Scholar]
  9. Fattaey A. R., Helin K., Dembski M. S., Dyson N., Harlow E., Vuocolo G. A., Hanobik M. G., Haskell K. M., Oliff A., Defeo-Jones D. Characterization of the retinoblastoma binding proteins RBP1 and RBP2. Oncogene. 1993 Nov;8(11):3149–3156. [PubMed] [Google Scholar]
  10. Fukunaga A., Tanaka A., Oishi K. Maleless, a recessive autosomal mutant of Drosophila melanogaster that specifically kills male zygotes. Genetics. 1975 Sep;81(1):135–141. doi: 10.1093/genetics/81.1.135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Georgakopoulos T., Thireos G. Two distinct yeast transcriptional activators require the function of the GCN5 protein to promote normal levels of transcription. EMBO J. 1992 Nov;11(11):4145–4152. doi: 10.1002/j.1460-2075.1992.tb05507.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Henikoff S., Henikoff J. G. Amino acid substitution matrices from protein blocks. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10915–10919. doi: 10.1073/pnas.89.22.10915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hilfiker A., Yang Y., Hayes D. H., Beard C. A., Manning J. E., Lucchesi J. C. Dosage compensation in Drosophila: the X-chromosomal binding of MSL-1 and MLE is dependent on Sxl activity. EMBO J. 1994 Aug 1;13(15):3542–3550. doi: 10.1002/j.1460-2075.1994.tb06661.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kamine J., Elangovan B., Subramanian T., Coleman D., Chinnadurai G. Identification of a cellular protein that specifically interacts with the essential cysteine region of the HIV-1 Tat transactivator. Virology. 1996 Feb 15;216(2):357–366. doi: 10.1006/viro.1996.0071. [DOI] [PubMed] [Google Scholar]
  15. Kelley R. L., Kuroda M. I. Equality for X chromosomes. Science. 1995 Dec 8;270(5242):1607–1610. doi: 10.1126/science.270.5242.1607. [DOI] [PubMed] [Google Scholar]
  16. Kelley R. L., Solovyeva I., Lyman L. M., Richman R., Solovyev V., Kuroda M. I. Expression of msl-2 causes assembly of dosage compensation regulators on the X chromosomes and female lethality in Drosophila. Cell. 1995 Jun 16;81(6):867–877. doi: 10.1016/0092-8674(95)90007-1. [DOI] [PubMed] [Google Scholar]
  17. Kleff S., Andrulis E. D., Anderson C. W., Sternglanz R. Identification of a gene encoding a yeast histone H4 acetyltransferase. J Biol Chem. 1995 Oct 20;270(42):24674–24677. doi: 10.1074/jbc.270.42.24674. [DOI] [PubMed] [Google Scholar]
  18. Koonin E. V., Zhou S., Lucchesi J. C. The chromo superfamily: new members, duplication of the chromo domain and possible role in delivering transcription regulators to chromatin. Nucleic Acids Res. 1995 Nov 11;23(21):4229–4233. doi: 10.1093/nar/23.21.4229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lu L., Berkey K. A., Casero R. A., Jr RGFGIGS is an amino acid sequence required for acetyl coenzyme A binding and activity of human spermidine/spermine N1acetyltransferase. J Biol Chem. 1996 Aug 2;271(31):18920–18924. doi: 10.1074/jbc.271.31.18920. [DOI] [PubMed] [Google Scholar]
  20. Reddy B. A., Kloc M., Etkin L. The cloning and characterization of a maternally expressed novel zinc finger nuclear phosphoprotein (xnf7) in Xenopus laevis. Dev Biol. 1991 Nov;148(1):107–116. doi: 10.1016/0012-1606(91)90321-s. [DOI] [PubMed] [Google Scholar]
  21. Reifsnyder C., Lowell J., Clarke A., Pillus L. Yeast SAS silencing genes and human genes associated with AML and HIV-1 Tat interactions are homologous with acetyltransferases. Nat Genet. 1996 Sep;14(1):42–49. doi: 10.1038/ng0996-42. [DOI] [PubMed] [Google Scholar]
  22. Richter L., Bone J. R., Kuroda M. I. RNA-dependent association of the Drosophila maleless protein with the male X chromosome. Genes Cells. 1996 Mar;1(3):325–336. doi: 10.1046/j.1365-2443.1996.26027.x. [DOI] [PubMed] [Google Scholar]
  23. Rubin G. M., Spradling A. C. Genetic transformation of Drosophila with transposable element vectors. Science. 1982 Oct 22;218(4570):348–353. doi: 10.1126/science.6289436. [DOI] [PubMed] [Google Scholar]
  24. Schuler G. D., Altschul S. F., Lipman D. J. A workbench for multiple alignment construction and analysis. Proteins. 1991;9(3):180–190. doi: 10.1002/prot.340090304. [DOI] [PubMed] [Google Scholar]
  25. Steinemann M., Steinemann S., Turner B. M. Evolution of dosage compensation. Chromosome Res. 1996 Apr;4(3):185–190. doi: 10.1007/BF02254957. [DOI] [PubMed] [Google Scholar]
  26. Turner B. M., Birley A. J., Lavender J. Histone H4 isoforms acetylated at specific lysine residues define individual chromosomes and chromatin domains in Drosophila polytene nuclei. Cell. 1992 Apr 17;69(2):375–384. doi: 10.1016/0092-8674(92)90417-b. [DOI] [PubMed] [Google Scholar]
  27. Wolffe A. P. Histone deacetylase: a regulator of transcription. Science. 1996 Apr 19;272(5260):371–372. doi: 10.1126/science.272.5260.371. [DOI] [PubMed] [Google Scholar]
  28. Wolffe A. P., Pruss D. Targeting chromatin disruption: Transcription regulators that acetylate histones. Cell. 1996 Mar 22;84(6):817–819. doi: 10.1016/s0092-8674(00)81059-4. [DOI] [PubMed] [Google Scholar]
  29. Yang X. J., Ogryzko V. V., Nishikawa J., Howard B. H., Nakatani Y. A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A. Nature. 1996 Jul 25;382(6589):319–324. doi: 10.1038/382319a0. [DOI] [PubMed] [Google Scholar]

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