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Genetics. 1999 May; 152(1): 249–268.
PMCID: PMC1460601

Role of the male specific lethal (msl) genes in modifying the effects of sex chromosomal dosage in Drosophila.


Immunostaining of chromosomes shows that the male-specific lethal (MSL) proteins are associated with all female chromosomes at a low level but are sequestered to the X chromosome in males. Histone-4 Lys-16 acetylation follows a similar pattern in normal males and females, being higher on the X and lower on the autosomes in males than in females. However, the staining pattern of acetylation and the mof gene product, a putative histone acetylase, in msl mutant males returns to a uniform genome-wide distribution as found in females. Gene expression on the autosomes correlates with the level of histone-4 acetylation. With minor exceptions, the expression levels of X-linked genes are maintained with either an increase or decrease of acetylation, suggesting that the MSL complex renders gene activity unresponsive to H4Lys16 acetylation. Evidence was also found for the presence of nucleation sites for association of the MSL proteins with the X chromosome rather than individual gene binding sequences. We suggest that sequestration of the MSL proteins occurs in males to nullify on the autosomes and maintain on the X, an inverse effect produced by negatively acting dosage-dependent regulatory genes as a consequence of the evolution of the X/Y sex chromosomal system.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Adler DA, Rugarli EI, Lingenfelter PA, Tsuchiya K, Poslinski D, Liggitt HD, Chapman VM, Elliott RW, Ballabio A, Disteche CM. 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. [PMC free article] [PubMed]
  • Datta S, Kankel DR. l(1)trol and l(1)devl, loci affecting the development of the adult central nervous system in Drosophila melanogaster. Genetics. 1992 Mar;130(3):523–537. [PMC free article] [PubMed]
  • Amrein H, Axel R. Genes expressed in neurons of adult male Drosophila. Cell. 1997 Feb 21;88(4):459–469. [PubMed]
  • Devlin RH, Holm DG, Grigliatti TA. Autosomal dosage compensation Drosophila melanogaster strains trisomic for the left arm of chromosome 2. Proc Natl Acad Sci U S A. 1982 Feb;79(4):1200–1204. [PMC free article] [PubMed]
  • Arkhipova I, Li J, Meselson M. On the mode of gene-dosage compensation in Drosophila. Genetics. 1997 Mar;145(3):729–736. [PMC free article] [PubMed]
  • Devlin RH, Holm DG, Grigliatti TA. The influence of whole-arm trisomy on gene expression in Drosophila. Genetics. 1988 Jan;118(1):87–101. [PMC free article] [PubMed]
  • Bashaw GJ, Baker BS. Dosage compensation and chromatin structure in Drosophila. Curr Opin Genet Dev. 1996 Aug;6(4):496–501. [PubMed]
  • Dorn R, Krauss V, Reuter G, Saumweber H. The enhancer of position-effect variegation of Drosophila, E(var)3-93D, codes for a chromatin protein containing a conserved domain common to several transcriptional regulators. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11376–11380. [PMC free article] [PubMed]
  • Bashaw GJ, Baker BS. 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. [PubMed]
  • Belote JM, Lucchesi JC. Control of X chromosome transcription by the maleless gene in Drosophila. Nature. 1980 Jun 19;285(5766):573–575. [PubMed]
  • Frolov MV, Benevolenskaya EV, Birchler JA. 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. [PMC free article] [PubMed]
  • Bhadra U, Pal-Bhadra M, Birchler JA. A trans-acting modifier causing extensive overexpression of genes in Drosophila melanogaster. Mol Gen Genet. 1997 May;254(6):621–634. [PubMed]
  • Bhadra U, Pal-Bhadra M, Birchler JA. A sex-influenced modifier in Drosophila that affects a broad spectrum of target loci including the histone repeats. Genetics. 1997 Jul;146(3):903–917. [PMC free article] [PubMed]
  • Giniger E, Tietje K, Jan LY, Jan YN. lola encodes a putative transcription factor required for axon growth and guidance in Drosophila. Development. 1994 Jun;120(6):1385–1398. [PubMed]
  • Graves JA, Disteche CM, Toder R. Gene dosage in the evolution and function of mammalian sex chromosomes. Cytogenet Cell Genet. 1998;80(1-4):94–103. [PubMed]
  • Grunstein M. Histone acetylation in chromatin structure and transcription. Nature. 1997 Sep 25;389(6649):349–352. [PubMed]
  • Birchler JA. 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. [PMC free article] [PubMed]
  • Guo M, Birchler JA. Trans-acting dosage effects on the expression of model gene systems in maize aneuploids. Science. 1994 Dec 23;266(5193):1999–2002. [PubMed]
  • Birchler JA. The genetic basis of dosage compensation of alcohol dehydrogenase-1 in maize. Genetics. 1981 Mar;97(3-4):625–637. [PMC free article] [PubMed]
  • Gutierrez AG, Christensen AC, Manning JE, Lucchesi JC. Cloning and dosage compensation of the 6-phosphogluconate dehydrogenase gene (Pgd+) of Drosophila melanogaster. Dev Genet. 1989;10(3):155–161. [PubMed]
  • Birchler JA. X chromosome dosage compensation in Drosophila. Science. 1996 May 24;272(5265):1190–1191. [PubMed]
  • Hazelrigg T, Levis R, Rubin GM. Transformation of white locus DNA in drosophila: dosage compensation, zeste interaction, and position effects. Cell. 1984 Feb;36(2):469–481. [PubMed]
  • Birchler JA, Newton KJ. Modulation of protein levels in chromosomal dosage series of maize: the biochemical basis of aneuploid syndromes. Genetics. 1981 Oct;99(2):247–266. [PMC free article] [PubMed]
  • Henikoff S. Dosage-dependent modification of position-effect variegation in Drosophila. Bioessays. 1996 May;18(5):401–409. [PubMed]
  • Birchler JA, Hiebert JC, Krietzman M. Gene expression in adult metafemales of Drosophila melanogaster. Genetics. 1989 Aug;122(4):869–879. [PMC free article] [PubMed]
  • Hiebert JC, Birchler JA. Dosage compensation of the copia retrotransposon in Drosophila melanogaster. Genetics. 1992 Mar;130(3):539–545. [PMC free article] [PubMed]
  • Birchler JA, Hiebert JC, Paigen K. Analysis of autosomal dosage compensation involving the alcohol dehydrogenase locus in Drosophila melanogaster. Genetics. 1990 Mar;124(3):679–686. [PMC free article] [PubMed]
  • Birchler JA, Bhadra U, Rabinow L, Linsk R, Nguyen-Huynh AT. Weakener of white (Wow), a gene that modifies the expression of the white eye color locus and that suppresses position effect variegation in Drosophila melanogaster. Genetics. 1994 Aug;137(4):1057–1070. [PMC free article] [PubMed]
  • Hilfiker A, Hilfiker-Kleiner D, Pannuti A, Lucchesi JC. 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. [PMC free article] [PubMed]
  • Bone JR, Lavender J, Richman R, Palmer MJ, Turner BM, Kuroda MI. Acetylated histone H4 on the male X chromosome is associated with dosage compensation in Drosophila. Genes Dev. 1994 Jan;8(1):96–104. [PubMed]
  • Kelley RL, Kuroda MI. Equality for X chromosomes. Science. 1995 Dec 8;270(5242):1607–1610. [PubMed]
  • Breen TR, Lucchesi JC. Analysis of the dosage compensation of a specific transcript in Drosophila melanogaster. Genetics. 1986 Mar;112(3):483–491. [PMC free article] [PubMed]
  • Kelley RL, Solovyeva I, Lyman LM, Richman R, Solovyev V, Kuroda MI. 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. [PubMed]
  • Chan CS, Rastelli L, Pirrotta V. A Polycomb response element in the Ubx gene that determines an epigenetically inherited state of repression. EMBO J. 1994 Jun 1;13(11):2553–2564. [PMC free article] [PubMed]
  • Krumm A, Roth GE, Korge G. Transformation of salivary gland secretion protein gene Sgs-4 in Drosophila: stage- and tissue-specific regulation, dosage compensation, and position effect. Proc Natl Acad Sci U S A. 1985 Aug;82(15):5055–5059. [PMC free article] [PubMed]
  • Charlesworth B. The evolution of sex chromosomes. Science. 1991 Mar 1;251(4997):1030–1033. [PubMed]
  • Kuroda MI, Kernan MJ, Kreber R, Ganetzky B, Baker BS. The maleless protein associates with the X chromosome to regulate dosage compensation in Drosophila. Cell. 1991 Sep 6;66(5):935–947. [PubMed]
  • Orr HA, Kim Y. An adaptive hypothesis for the evolution of the Y chromosome. Genetics. 1998 Dec;150(4):1693–1698. [PMC free article] [PubMed]
  • Laurie-Ahlberg CC, Stam LF. Use of P-element-mediated transformation to identify the molecular basis of naturally occurring variants affecting Adh expression in Drosophila melanogaster. Genetics. 1987 Jan;115(1):129–140. [PMC free article] [PubMed]
  • Pal Bhadra M, Bhadra U, Birchler JA. Role of multiple trans-acting regulators in modifying the effect of the retrotransposon copia on host gene expression in Drosophila. Mol Gen Genet. 1998 Aug;259(2):198–206. [PubMed]
  • Lucchesi JC, Manning JE. Gene dosage compensation in Drosophila melanogaster. Adv Genet. 1987;24:371–429. [PubMed]
  • Qian S, Pirrotta V. Dosage compensation of the Drosophila white gene requires both the X chromosome environment and multiple intragenic elements. Genetics. 1995 Feb;139(2):733–744. [PMC free article] [PubMed]
  • Rabinow L, Nguyen-Huynh AT, Birchler JA. 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. [PMC free article] [PubMed]
  • Lucchesi JC, Rawls RM., Jr Regulation of gene function: a comparison of X-linked enzyme activity levels in normal and intersexual triploids of Drosophila melanogaster. Genetics. 1973 Mar;73(3):459–464. [PMC free article] [PubMed]
  • Roseman RR, Swan JM, Geyer PK. A Drosophila insulator protein facilitates dosage compensation of the X chromosome min-white gene located at autosomal insertion sites. Development. 1995 Nov;121(11):3573–3582. [PubMed]
  • Lucchesi JC, Rawls JM, Jr, Maroni G. Gene dosage compensation in metafemales (3X;2A) of Drosophila. Nature. 1974 Apr 12;248(449):564–567. [PubMed]
  • Sass H, Meselson M. Dosage compensation of the Drosophila pseudoobscura Hsp82 gene and the Drosophila melanogaster Adh gene at ectopic sites in D. melanogaster. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6795–6799. [PMC free article] [PubMed]
  • Mann R, Hake L, Lucchesi JC. Phenogenetics of triploid intersexes in Drosophila melanogaster. Dev Genet. 1986;6(4):247–255. [PubMed]
  • Scott MJ, Lucchesi JC. Structure and expression of the Drosophila melanogaster gene encoding 6-phosphogluconate dehydrogenase. Gene. 1991 Dec 30;109(2):177–183. [PubMed]
  • Marcand S, Buck SW, Moretti P, Gilson E, Shore D. Silencing of genes at nontelomeric sites in yeast is controlled by sequestration of silencing factors at telomeres by Rap 1 protein. Genes Dev. 1996 Jun 1;10(11):1297–1309. [PubMed]
  • Spradling AC, Rubin GM. The effect of chromosomal position on the expression of the Drosophila xanthine dehydrogenase gene. Cell. 1983 Aug;34(1):47–57. [PubMed]
  • Marín I, Franke A, Bashaw GJ, Baker BS. The dosage compensation system of Drosophila is co-opted by newly evolved X chromosomes. Nature. 1996 Sep 12;383(6596):160–163. [PubMed]
  • Turner BM, Birley AJ, 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. [PubMed]
  • Meller VH, Wu KH, Roman G, Kuroda MI, Davis RL. 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. [PubMed]
  • Wolffe AP, Pruss D. Targeting chromatin disruption: Transcription regulators that acetylate histones. Cell. 1996 Mar 22;84(6):817–819. [PubMed]
  • Zhou S, Yang Y, Scott MJ, Pannuti A, Fehr KC, Eisen A, Koonin EV, Fouts DL, Wrightsman R, Manning JE, et al. Male-specific lethal 2, a dosage compensation gene of Drosophila, undergoes sex-specific regulation and encodes a protein with a RING finger and a metallothionein-like cysteine cluster. EMBO J. 1995 Jun 15;14(12):2884–2895. [PMC free article] [PubMed]

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