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Gene Review

msl-1  -  male-specific lethal 1

Drosophila melanogaster

Synonyms: CG10385, Dmel\CG10385, MSL, MSL-1, MSL1, ...
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High impact information on msl-1


Biological context of msl-1

  • Dosage compensation in Drosophila occurs by a twofold increase in transcription per copy of X-linked genes in males (XY) compared with females (XX). msl-1 is one of four genes that are essential for dosage compensation in males, and MSL-1 protein is associated specifically with the male X chromosome [4].
  • Two of the msls, the mle and msl-1 genes, encode proteins that are associated with hundreds of specific sites along the length of the male X chromosome [5].
  • A delayed onset of binding of the MSLs in male progeny of homozygous mutant msl-1 or mle mothers coupled with the previous finding that such males have an earlier lethal phase supports the idea that msl-mediated dosage compensation begins early in embryogenesis [6].
  • Drosophila male-specific lethal-2 protein: structure/function analysis and dependence on MSL-1 for chromosome association [7].
  • The results are as follows: the msl-1 and msl-2 genes are not needed in the germline, while the mle gene seems to be required for normal spermatogenesis [8].

Anatomical context of msl-1

  • In wildtype males, binding of the MSL-1 gene product to the X chromosome is first seen at the cellular blastoderm stage (stage 5) [9].
  • MSL test results in spermatogonia and postspermatogonia were also compared separately to the SLRL, UDS, and AE assays [10].

Associations of msl-1 with chemical compounds

  • The amino-terminal region of Drosophila MSL1 contains basic, glycine-rich, and leucine zipper-like motifs that promote X chromosome binding, self-association, and MSL2 binding, respectively [11].
  • Three of these proteins, MLE, MSL-1 and histone H4 acetylated at lysine 16 (H4Ac16), have recently been shown to be located almost exclusively on the male X chromosome in interphase (polytene) cells [12].

Physical interactions of msl-1

  • MLE and MSL-1 X chromosome binding are negatively regulated by Sxl in females and require the functions of the other msls in males [5].

Regulatory relationships of msl-1

  • MSL-1 protein levels are negatively regulated by Sxl in females, resulting in male-specific expression of MSL-1 [4].

Other interactions of msl-1

  • In addition, msl-2 is required for translation and/or stability of MSL-1 in males [4].
  • We showed previously that MSL3 is essential for the activation of MOF's nucleosomal histone acetyltransferase activity within an MSL1-MOF complex [13].
  • Interaction with MSL1 mediates the activation of MOF in vitro and the targeting of MSL3 to the X-chromosomal territory in vivo [13].
  • Early binding of MSL-1 is never seen in wildtype female embryos, and we have determined that this inhibition is mediated by the SXL product made by the activation of the early Sxl promoter [9].


  1. X-chromosome-wide profiling of MSL-1 distribution and dosage compensation in Drosophila. Legube, G., McWeeney, S.K., Lercher, M.J., Akhtar, A. Genes Dev. (2006) [Pubmed]
  2. Chromosome-wide gene-specific targeting of the Drosophila dosage compensation complex. Gilfillan, G.D., Straub, T., de Wit, E., Greil, F., Lamm, R., van Steensel, B., Becker, P.B. Genes Dev. (2006) [Pubmed]
  3. Global regulation of X chromosomal genes by the MSL complex in Drosophila melanogaster. Hamada, F.N., Park, P.J., Gordadze, P.R., Kuroda, M.I. Genes Dev. (2005) [Pubmed]
  4. Sex-specific regulation of the male-specific lethal-1 dosage compensation gene in Drosophila. Palmer, M.J., Richman, R., Richter, L., Kuroda, M.I. Genes Dev. (1994) [Pubmed]
  5. Molecular characterization of the male-specific lethal-3 gene and investigations of the regulation of dosage compensation in Drosophila. Gorman, M., Franke, A., Baker, B.S. Development (1995) [Pubmed]
  6. Evidence that MSL-mediated dosage compensation in Drosophila begins at blastoderm. Franke, A., Dernburg, A., Bashaw, G.J., Baker, B.S. Development (1996) [Pubmed]
  7. Drosophila male-specific lethal-2 protein: structure/function analysis and dependence on MSL-1 for chromosome association. Lyman, L.M., Copps, K., Rastelli, L., Kelley, R.L., Kuroda, M.I. Genetics (1997) [Pubmed]
  8. Mutations affecting dosage compensation in Drosophila melanogaster: effects in the germline. Bachiller, D., Sánchez, L. Dev. Biol. (1986) [Pubmed]
  9. Dosage compensation in Drosophila: the X chromosome binding of MSL-1 and MSL-2 in female embryos is prevented by the early expression of the Sxl gene. McDowell, K.A., Hilfiker, A., Lucchesi, J.C. Mech. Dev. (1996) [Pubmed]
  10. Assessing the risk of heritable gene mutation in mammals: drosophila sex-linked recessive lethal test and tests measuring DNA damage and repair in mammalian germ cells. Bentley, K.S., Sarrif, A.M., Cimino, M.C., Auletta, A.E. Environ. Mol. Mutagen. (1994) [Pubmed]
  11. The amino-terminal region of Drosophila MSL1 contains basic, glycine-rich, and leucine zipper-like motifs that promote X chromosome binding, self-association, and MSL2 binding, respectively. Li, F., Parry, D.A., Scott, M.J. Mol. Cell. Biol. (2005) [Pubmed]
  12. Histone H4 acetylated at lysine 16 and proteins of the Drosophila dosage compensation pathway co-localize on the male X chromosome through mitosis. Lavender, J.S., Birley, A.J., Palmer, M.J., Kuroda, M.I., Turner, B.M. Chromosome Res. (1994) [Pubmed]
  13. The MRG domain mediates the functional integration of MSL3 into the dosage compensation complex. Morales, V., Regnard, C., Izzo, A., Vetter, I., Becker, P.B. Mol. Cell. Biol. (2005) [Pubmed]
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