Msl1-mediated dimerization of the dosage compensation complex is essential for male X-chromosome regulation in Drosophila

Mol Cell. 2012 Nov 30;48(4):587-600. doi: 10.1016/j.molcel.2012.09.014. Epub 2012 Oct 18.


The Male-Specific Lethal (MSL) complex regulates dosage compensation of the male X chromosome in Drosophila. Here, we report the crystal structure of its MSL1/MSL2 core, where two MSL2 subunits bind to a dimer formed by two molecules of MSL1. Analysis of structure-based mutants revealed that MSL2 can only interact with the MSL1 dimer, but MSL1 dimerization is MSL2 independent. We show that Msl1 is a substrate for Msl2 E3 ubiquitin ligase activity. ChIP experiments revealed that Msl1 dimerization is essential for targeting and spreading of the MSL complex on X-linked genes; however, Msl1 binding to promoters of male and female cells is independent of the dimer status and other MSL proteins. Finally, we show that loss of Msl1 dimerization leads to male-specific lethality. We propose that Msl1-mediated dimerization of the entire MSL complex is required for Msl2 binding, X chromosome recognition, and spreading along the X chromosome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / isolation & purification
  • DNA-Binding Proteins / metabolism
  • Dosage Compensation, Genetic*
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / isolation & purification
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism*
  • Male
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / isolation & purification
  • Nuclear Proteins / metabolism*
  • Protein Multimerization
  • Transcription Factors / chemistry
  • Transcription Factors / isolation & purification
  • Transcription Factors / metabolism*
  • X Chromosome / genetics*
  • X Chromosome / metabolism*


  • DNA-Binding Proteins
  • Drosophila Proteins
  • Nuclear Proteins
  • Transcription Factors
  • msl-1 protein, Drosophila
  • msl-2 protein, Drosophila

Associated data

  • PDB/4B7Y
  • PDB/4B86