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.
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.
Zhou
S
S
Department of Biology, Emory University, Atlanta, GA 30322, USA.
Yang
Y
Y
Scott
M J
MJ
Pannuti
A
A
Fehr
K C
KC
Eisen
A
A
Koonin
E V
EV
Fouts
D L
DL
Wrightsman
R
R
Manning
J E
JE
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016386:Chromosome Walking; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins; D004303:Dosage Compensation, Genetic; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins; D005260:Female; D017344:Genes, Insect / Q000235:genetics*; D005809:Genes, Regulator / Q000235:genetics*; D007526:Isoelectric Point; D008297:Male; D008668:Metallothionein / Q000235:genetics; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D009690:Nucleic Acid Conformation; D012326:RNA Splicing; D012333:RNA, Messenger / Q000032:analysis / Q000737:chemistry; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics*
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C094166:msl-2 protein, Drosophila; D008668:Metallothionein