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. 2000 Jun;155(2):753–763. doi: 10.1093/genetics/155.2.753

Histone acetylation and gene expression analysis of sex lethal mutants in Drosophila.

U Bhadra 1, M Pal-Bhadra 1, J A Birchler 1
PMCID: PMC1461119  PMID: 10835396

Abstract

The evolution of sex determination mechanisms is often accompanied by reduction in dosage of genes on a whole chromosome. Under these circumstances, negatively acting regulatory genes would tend to double the expression of the genome, which produces compensation of the single-sex chromosome and increases autosomal gene expression. Previous work has suggested that to reduce the autosomal expression to the female level, these dosage effects are modified by a chromatin complex specific to males, which sequesters a histone acetylase to the X. The reduced autosomal histone 4 lysine 16 (H4Lys16) acetylation results in lowered autosomal expression, while the higher acetylation on the X is mitigated by the male-specific lethal complex, preventing overexpression. In this report, we examine how mutations in the principal sex determination gene, Sex lethal (Sxl), impact the H4 acetylation and gene expression on both the X and autosomes. When Sxl expression is missing in females, we find that the sequestration occurs concordantly with reductions in autosomal H4Lys16 acetylation and gene expression on the whole. When Sxl is ectopically expressed in Sxl(M) mutant males, the sequestration is disrupted, leading to an increase in autosomal H4Lys16 acetylation and overall gene expression. In both cases we find relatively little effect upon X chromosomal gene expression.

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Selected References

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  1. Adler D. A., Rugarli E. I., Lingenfelter P. A., Tsuchiya K., Poslinski D., Liggitt H. D., Chapman V. M., Elliott R. W., Ballabio A., Disteche C. M. Evidence of evolutionary up-regulation of the single active X chromosome in mammals based on Clc4 expression levels in Mus spretus and Mus musculus. Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9244–9248. doi: 10.1073/pnas.94.17.9244. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Amrein H., Axel R. Genes expressed in neurons of adult male Drosophila. Cell. 1997 Feb 21;88(4):459–469. doi: 10.1016/s0092-8674(00)81886-3. [DOI] [PubMed] [Google Scholar]
  3. Arkhipova I., Li J., Meselson M. On the mode of gene-dosage compensation in Drosophila. Genetics. 1997 Mar;145(3):729–736. doi: 10.1093/genetics/145.3.729. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Bashaw G. J., Baker B. S. The msl-2 dosage compensation gene of Drosophila encodes a putative DNA-binding protein whose expression is sex specifically regulated by Sex-lethal. Development. 1995 Oct;121(10):3245–3258. doi: 10.1242/dev.121.10.3245. [DOI] [PubMed] [Google Scholar]
  6. Bashaw G. J., Baker B. S. The regulation of the Drosophila msl-2 gene reveals a function for Sex-lethal in translational control. Cell. 1997 May 30;89(5):789–798. doi: 10.1016/s0092-8674(00)80262-7. [DOI] [PubMed] [Google Scholar]
  7. Bell L. R., Horabin J. I., Schedl P., Cline T. W. Positive autoregulation of sex-lethal by alternative splicing maintains the female determined state in Drosophila. Cell. 1991 Apr 19;65(2):229–239. doi: 10.1016/0092-8674(91)90157-t. [DOI] [PubMed] [Google Scholar]
  8. Bernstein M., Lersch R. A., Subrahmanyan L., Cline T. W. Transposon insertions causing constitutive Sex-lethal activity in Drosophila melanogaster affect Sxl sex-specific transcript splicing. Genetics. 1995 Feb;139(2):631–648. doi: 10.1093/genetics/139.2.631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bhadra U., Pal-Bhadra M., Birchler J. A. A trans-acting modifier causing extensive overexpression of genes in Drosophila melanogaster. Mol Gen Genet. 1997 May;254(6):621–634. doi: 10.1007/s004380050460. [DOI] [PubMed] [Google Scholar]
  10. Bhadra U., Pal-Bhadra M., Birchler J. A. Role of the male specific lethal (msl) genes in modifying the effects of sex chromosomal dosage in Drosophila. Genetics. 1999 May;152(1):249–268. doi: 10.1093/genetics/152.1.249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Birchler J. A. A study of enzyme activities in a dosage series of the long arm of chromosome one in maize. Genetics. 1979 Aug;92(4):1211–1229. doi: 10.1093/genetics/92.4.1211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Birchler J. A. Expression of cis-regulatory mutations of the white locus in metafemales of Drosophila melanogaster. Genet Res. 1992 Feb;59(1):11–18. doi: 10.1017/s0016672300030123. [DOI] [PubMed] [Google Scholar]
  13. Birchler J. A., Newton K. J. Modulation of protein levels in chromosomal dosage series of maize: the biochemical basis of aneuploid syndromes. Genetics. 1981 Oct;99(2):247–266. doi: 10.1093/genetics/99.2.247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Charlesworth B. The evolution of chromosomal sex determination and dosage compensation. Curr Biol. 1996 Feb 1;6(2):149–162. doi: 10.1016/s0960-9822(02)00448-7. [DOI] [PubMed] [Google Scholar]
  15. Cline T. W. Evidence that sisterless-a and sisterless-b are two of several discrete "numerator elements" of the X/A sex determination signal in Drosophila that switch Sxl between two alternative stable expression states. Genetics. 1988 Aug;119(4):829–862. doi: 10.1093/genetics/119.4.829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Devlin R. H., Holm D. G., Grigliatti T. A. The influence of whole-arm trisomy on gene expression in Drosophila. Genetics. 1988 Jan;118(1):87–101. doi: 10.1093/genetics/118.1.87. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Erickson J. W., Cline T. W. A bZIP protein, sisterless-a, collaborates with bHLH transcription factors early in Drosophila development to determine sex. Genes Dev. 1993 Sep;7(9):1688–1702. doi: 10.1101/gad.7.9.1688. [DOI] [PubMed] [Google Scholar]
  18. Franke A., Baker B. S. The rox1 and rox2 RNAs are essential components of the compensasome, which mediates dosage compensation in Drosophila. Mol Cell. 1999 Jul;4(1):117–122. doi: 10.1016/s1097-2765(00)80193-8. [DOI] [PubMed] [Google Scholar]
  19. Frolov M. V., Benevolenskaya E. V., Birchler J. A. Regena (Rga), a Drosophila homolog of the global negative transcriptional regulator CDC36 (NOT2) from yeast, modifies gene expression and suppresses position effect variegation. Genetics. 1998 Jan;148(1):317–329. doi: 10.1093/genetics/148.1.317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Gorman M., Kuroda M. I., Baker B. S. Regulation of the sex-specific binding of the maleless dosage compensation protein to the male X chromosome in Drosophila. Cell. 1993 Jan 15;72(1):39–49. doi: 10.1016/0092-8674(93)90048-u. [DOI] [PubMed] [Google Scholar]
  21. Guo M., Birchler J. A. Trans-acting dosage effects on the expression of model gene systems in maize aneuploids. Science. 1994 Dec 23;266(5193):1999–2002. doi: 10.1126/science.266.5193.1999. [DOI] [PubMed] [Google Scholar]
  22. Henikoff S. Dosage-dependent modification of position-effect variegation in Drosophila. Bioessays. 1996 May;18(5):401–409. doi: 10.1002/bies.950180510. [DOI] [PubMed] [Google Scholar]
  23. Henikoff S. Position Effects and Variegation Enhancers in an Autosomal Region of DROSOPHILA MELANOGASTER. Genetics. 1979 Sep;93(1):105–115. doi: 10.1093/genetics/93.1.105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hiebert J. C., Birchler J. A. Effects of the maleless mutation on X and autosomal gene expression in Drosophila melanogaster. Genetics. 1994 Mar;136(3):913–926. doi: 10.1093/genetics/136.3.913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hilfiker A., Hilfiker-Kleiner D., Pannuti A., Lucchesi J. C. 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. EMBO J. 1997 Apr 15;16(8):2054–2060. doi: 10.1093/emboj/16.8.2054. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Jin Y., Wang Y., Walker D. L., Dong H., Conley C., Johansen J., Johansen K. M. JIL-1: a novel chromosomal tandem kinase implicated in transcriptional regulation in Drosophila. Mol Cell. 1999 Jul;4(1):129–135. doi: 10.1016/s1097-2765(00)80195-1. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Kelley R. L., Meller V. H., Gordadze P. R., Roman G., Davis R. L., Kuroda M. I. Epigenetic spreading of the Drosophila dosage compensation complex from roX RNA genes into flanking chromatin. Cell. 1999 Aug 20;98(4):513–522. doi: 10.1016/s0092-8674(00)81979-0. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Kelley R. L., Wang J., Bell L., Kuroda M. I. Sex lethal controls dosage compensation in Drosophila by a non-splicing mechanism. Nature. 1997 May 8;387(6629):195–199. doi: 10.1038/387195a0. [DOI] [PubMed] [Google Scholar]
  31. Kuroda M. I., Kernan M. J., Kreber R., Ganetzky B., Baker B. S. The maleless protein associates with the X chromosome to regulate dosage compensation in Drosophila. Cell. 1991 Sep 6;66(5):935–947. doi: 10.1016/0092-8674(91)90439-6. [DOI] [PubMed] [Google Scholar]
  32. Lucchesi J. C., Skripsky T. The link between dosage compensation and sex differentiation in Drosophila melanogaster. Chromosoma. 1981;82(2):217–227. doi: 10.1007/BF00286106. [DOI] [PubMed] [Google Scholar]
  33. Lyman L. M., Copps K., Rastelli L., Kelley R. L., Kuroda M. I. Drosophila male-specific lethal-2 protein: structure/function analysis and dependence on MSL-1 for chromosome association. Genetics. 1997 Dec;147(4):1743–1753. doi: 10.1093/genetics/147.4.1743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Meller V. H., Wu K. H., Roman G., Kuroda M. I., Davis R. L. roX1 RNA paints the X chromosome of male Drosophila and is regulated by the dosage compensation system. Cell. 1997 Feb 21;88(4):445–457. doi: 10.1016/s0092-8674(00)81885-1. [DOI] [PubMed] [Google Scholar]
  35. Rabinow L., Nguyen-Huynh A. T., Birchler J. A. A trans-acting regulatory gene that inversely affects the expression of the white, brown and scarlet loci in Drosophila. Genetics. 1991 Oct;129(2):463–480. doi: 10.1093/genetics/129.2.463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. 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]

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