The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
Gene Review

msl-2  -  male-specific lethal 2

Drosophila melanogaster

Synonyms: CG3241, Dmel\CG3241, E3 ubiquitin-protein ligase msl-2, MSL, MSL-2, ...
 
 
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.
 

Disease relevance of msl-2

 

High impact information on msl-2

  • Female flies must inhibit msl-2 mRNA translation for survival, and this inhibition is mediated by Sex-lethal (SXL) binding to sites in both the 5' and the 3' untranslated regions (UTRs) [2].
  • A dual inhibitory mechanism restricts msl-2 mRNA translation for dosage compensation in Drosophila [2].
  • The multisubunit MSL dosage compensation complex binds to hundreds of sites along the Drosophila single male X chromosome, mediating its hypertranscription [3].
  • Consistent with the formation of a dosage compensation protein complex, msl-2 colocalizes with the other MSL proteins on the male X chromosome and coimmunoprecipitates with msl-1 from male larval extracts [4].
  • In this neo-X chromosome, the pattern of MSL binding correlates with the known pattern of dosage compensation [5].
 

Biological context of msl-2

  • Expression of msl-2 causes assembly of dosage compensation regulators on the X chromosomes and female lethality in Drosophila [4].
  • An intron present at the 5' untranslated region (UTR) of msl-2 mRNA contains putative SXL binding sites and is retained in female flies [6].
  • We also used three strains that carried constitutive transgenes of msl-2 with mutations in the 5' untranslated regions [7].
  • The encoded protein (MSL-2) consists of 769 amino acid residues and has a RING finger (C3HC4 zinc finger) and a metallothionein-like domain with eight conserved and two non-conserved cysteines [8].
  • A human protein complex homologous to the Drosophila MSL complex is responsible for the majority of histone H4 acetylation at lysine 16 [9].
 

Anatomical context of msl-2

  • MSL-2 lacks a maternal component, and male-specific zygotic expression is detectable at the end of blastoderm [10].
  • These results reveal an unexpected physical and functional connection between nuclear pore components and chromatin regulation through MSL proteins, highlighting the role of nucleoporins in gene regulation in higher eukaryotes [11].
  • Here, we report the purification of enzymatically active MSL complexes from Drosophila embryos, Schneider cells, and human HeLa cells [11].
  • This distribution pattern has been interpreted as a reflection of the tissue-specific transcriptional activity of the larval salivary gland and as an indication that the MSL complex associates with active chromatin [12].
  • We observed that MLE is the only MSL expressed in the male germ cells and it is not localized to the X chromosome [13].
 

Associations of msl-2 with chemical compounds

  • 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 [8].
  • Although UNR is present in both male and female flies, binding of SXL to uridine-rich sequences in the 3' untranslated region (UTR) of msl-2 mRNA recruits UNR to adjacent regulatory sequences, thereby conferring a sex-specific function to UNR [14].
  • We propose that the basic region may mediate DNA binding and that the glycine-rich region may promote the association of MSL complexes to closely adjacent sites on the X chromosome [15].
  • X chromosome binding also requires a conserved leucine zipper-like motif that binds to MSL2 [15].
 

Physical interactions of msl-2

  • The msl-2 dosage compensation gene of Drosophila encodes a putative DNA-binding protein whose expression is sex specifically regulated by Sex-lethal [16].
 

Regulatory relationships of msl-2

  • We also provide evidence that the repression of MSL-2 is directly regulated by Sex-lethal at the level of translation [17].
 

Other interactions of msl-2

  • In addition, msl-2 is required for translation and/or stability of MSL-1 in males [18].
  • Our observations suggest that MSL-2 may be the target of the master regulatory gene Sxl and provide the basic elements of a working hypothesis on the function of MSL-2 in mediating the 2-fold increase in transcription that is characteristic of dosage compensation [8].
  • We also used site-directed mutagenesis to determine the importance of the MSL-2 RING finger domain and second cysteine-rich motif [19].
  • The MSL-2 protein is the only one found in Drosophila and vertebrate genomes that contains both a RING finger and a peculiar type of CXC domain, related to the one present in Enhancer of Zeste proteins [20].
  • These mutations are the male-specific lethals msl-1, msl-2, and mle, which have been analyzed in the somatic tissues [21].
 

Analytical, diagnostic and therapeutic context of msl-2

References

  1. Association and spreading of the Drosophila dosage compensation complex from a discrete roX1 chromatin entry site. Kageyama, Y., Mengus, G., Gilfillan, G., Kennedy, H.G., Stuckenholz, C., Kelley, R.L., Becker, P.B., Kuroda, M.I. EMBO J. (2001) [Pubmed]
  2. A dual inhibitory mechanism restricts msl-2 mRNA translation for dosage compensation in Drosophila. Beckmann, K., Grskovic, M., Gebauer, F., Hentze, M.W. Cell (2005) [Pubmed]
  3. Epigenetic spreading of the Drosophila dosage compensation complex from roX RNA genes into flanking chromatin. Kelley, R.L., Meller, V.H., Gordadze, P.R., Roman, G., Davis, R.L., Kuroda, M.I. Cell (1999) [Pubmed]
  4. Expression of msl-2 causes assembly of dosage compensation regulators on the X chromosomes and female lethality in Drosophila. Kelley, R.L., Solovyeva, I., Lyman, L.M., Richman, R., Solovyev, V., Kuroda, M.I. Cell (1995) [Pubmed]
  5. The dosage compensation system of Drosophila is co-opted by newly evolved X chromosomes. Marín, I., Franke, A., Bashaw, G.J., Baker, B.S. Nature (1996) [Pubmed]
  6. The Drosophila splicing regulator sex-lethal directly inhibits translation of male-specific-lethal 2 mRNA. Gebauer, F., Merendino, L., Hentze, M.W., Valcárcel, J. RNA (1998) [Pubmed]
  7. Dosage compensation and intercalary heterochromatin in X chromosomes of Drosophila melanogaster. Alekseyenko, A.A., Demakova, O.V., Belyaeva, E.S., Makarevich, G.F., Kotlikova, I.V., Nöthiger, R., Zhimulev, I.F. Chromosoma (2002) [Pubmed]
  8. 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. Zhou, S., Yang, Y., Scott, M.J., Pannuti, A., Fehr, K.C., Eisen, A., Koonin, E.V., Fouts, D.L., Wrightsman, R., Manning, J.E. EMBO J. (1995) [Pubmed]
  9. A human protein complex homologous to the Drosophila MSL complex is responsible for the majority of histone H4 acetylation at lysine 16. Smith, E.R., Cayrou, C., Huang, R., Lane, W.S., Côté, J., Lucchesi, J.C. Mol. Cell. Biol. (2005) [Pubmed]
  10. The dosage compensation regulators MLE, MSL-1 and MSL-2 are interdependent since early embryogenesis in Drosophila. Rastelli, L., Richman, R., Kuroda, M.I. Mech. Dev. (1995) [Pubmed]
  11. Nuclear pore components are involved in the transcriptional regulation of dosage compensation in Drosophila. Mendjan, S., Taipale, M., Kind, J., Holz, H., Gebhardt, P., Schelder, M., Vermeulen, M., Buscaino, A., Duncan, K., Mueller, J., Wilm, M., Stunnenberg, H.G., Saumweber, H., Akhtar, A. Mol. Cell (2006) [Pubmed]
  12. Male-specific lethal complex of Drosophila targets activated regions of the X chromosome for chromatin remodeling. Sass, G.L., Pannuti, A., Lucchesi, J.C. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  13. An analysis of maleless and histone H4 acetylation in Drosophila melanogaster spermatogenesis. Rastelli, L., Kuroda, M.I. Mech. Dev. (1998) [Pubmed]
  14. Drosophila UNR is required for translational repression of male-specific lethal 2 mRNA during regulation of X-chromosome dosage compensation. Abaza, I., Coll, O., Patalano, S., Gebauer, F. Genes Dev. (2006) [Pubmed]
  15. 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]
  16. The msl-2 dosage compensation gene of Drosophila encodes a putative DNA-binding protein whose expression is sex specifically regulated by Sex-lethal. Bashaw, G.J., Baker, B.S. Development (1995) [Pubmed]
  17. The regulation of the Drosophila msl-2 gene reveals a function for Sex-lethal in translational control. Bashaw, G.J., Baker, B.S. Cell (1997) [Pubmed]
  18. 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]
  19. 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]
  20. Evolution of chromatin-remodeling complexes: comparative genomics reveals the ancient origin of "novel" compensasome genes. Marín, I. J. Mol. Evol. (2003) [Pubmed]
  21. Mutations affecting dosage compensation in Drosophila melanogaster: effects in the germline. Bachiller, D., Sánchez, L. Dev. Biol. (1986) [Pubmed]
  22. Linking global histone acetylation to the transcription enhancement of X-chromosomal genes in Drosophila males. Smith, E.R., Allis, C.D., Lucchesi, J.C. J. Biol. Chem. (2001) [Pubmed]
 
WikiGenes - Universities