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):2884-95.


In Drosophila the equalization of X-linked gene products between males and females, i.e. dosage compensation, is the result of a 2-fold hypertranscription of most of these genes in males. At least four regulatory genes are required for this process. Three of these genes, maleless (mle), male-specific lethal 1 (msl-1) and male-specific lethal 3 (msl-3), have been cloned and their products have been shown to interact and to bind to numerous sites on the X chromosome of males, but not of females. Although binding to the X chromosome is negatively correlated with the function of the master regulatory gene Sex lethal (Sxl), the mechanisms that restrict this binding to males and to the X chromosome are not yet understood. We have cloned the last of the known autosomal genes involved in dosage compensation, male-specific lethal 2 (msl-2), and characterized its product. 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. In addition, it contains a positively and a negatively charged amino acid residue cluster and a coiled coil domain that may be involved in protein-protein interactions. Males produce a msl-2 transcript that is shorter than in females, due to differential splicing of an intron of 132 bases in the untranslated leader. Using an antiserum against MSL-2 we have shown that the protein is expressed at a detectable level only in males, where it is physically associated with the X chromosome. 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Chromosome Walking
  • Cloning, Molecular
  • DNA-Binding Proteins
  • Dosage Compensation, Genetic*
  • Drosophila / genetics
  • Drosophila Proteins
  • Female
  • Genes, Insect / genetics*
  • Genes, Regulator / genetics*
  • Isoelectric Point
  • Male
  • Metallothionein / genetics
  • Molecular Sequence Data
  • Molecular Weight
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics*
  • Nucleic Acid Conformation
  • RNA Splicing
  • RNA, Messenger / analysis
  • RNA, Messenger / chemistry
  • Sequence Analysis, DNA
  • Transcription Factors / chemistry
  • Transcription Factors / genetics*
  • Zinc Fingers / genetics*


  • DNA-Binding Proteins
  • Drosophila Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • Transcription Factors
  • msl-2 protein, Drosophila
  • Metallothionein

Associated data

  • GENBANK/Z48443