X-chromosome targeting and dosage compensation are mediated by distinct domains in MSL-3

EMBO Rep. 2006 May;7(5):531-8. doi: 10.1038/sj.embor.7400658. Epub 2006 Mar 10.


In Drosophila, dosage compensation of X-linked genes is achieved by transcriptional upregulation of the male X chromosome. Genetic and biochemical studies have demonstrated that male-specific lethal (MSL) proteins together with roX RNAs regulate this process. Here, we show that MSL-3 is essential for cell viability and that three domains in the protein have distinct roles in dosage compensation. The chromo-barrel domain (CBD) is not necessary for MSL targeting to the male X chromosome but is important for male viability and equalization of X-linked gene transcription. The polar region cooperates with the CBD in MSL-3 function, whereas the MRG domain is responsible for targeting the protein to the X chromosome. Our results demonstrate that MSL-3 localization to the male X chromosome and transcriptional upregulation of X-linked genes are two separable functions of the MSL-3 protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs / genetics
  • Animals
  • Animals, Genetically Modified
  • Dosage Compensation, Genetic / physiology*
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / physiology*
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism*
  • Female
  • Gene Targeting
  • Male
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / physiology*
  • Protein Structure, Tertiary / genetics
  • Transcription Factors / chemistry
  • Transcription Factors / physiology*
  • Transcription, Genetic
  • Up-Regulation / genetics
  • X Chromosome / genetics
  • X Chromosome / metabolism*


  • Drosophila Proteins
  • Nuclear Proteins
  • Transcription Factors
  • msl-3 protein, Drosophila