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.

Abstract

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.

The Drosophila DAXX-Like Protein (DLP) Cooperates with ASF1 for H3.3 Deposition and Heterochromatin Formation

“…MSL-2 is expressed only in males (39) and induces the assembly of the MSL complex on chromatin and a 2-fold upregulation of the single X chromosome to reach the level of the two X chromosomes in females (33). We then investigated the consequences of overexpressed dlp for male viability when msl-2 function is reduced (Fig.…”

Chromosome-wide gene-specific targeting of theDrosophiladosage compensation complex

“…MSL1 is arguably the best marker of DCC binding, as MSL1 and MSL2 have been suggested to form the DNA-binding "core" of the DCC (Lyman et al 1997) and MSL1 consistently gave the most robust ChIP signals. While MSL2 is the only DCC member with a strictly male expression (Bashaw and Baker 1995;Zhou et al 1995), MSL1 is inherently unstable in the absence of MSL2 and the DCC does not form in females (Gilfillan et al 2004). This permitted the use of mixed male and female wild-type embryos, as females are expected to contribute only background signals to any ChIP with MSL1.…”

Evolution of Chromatin-Remodeling Complexes: Comparative Genomics Reveals the Ancient Origin of "Novel" Compensasome Genes

“…1A, the most similar regions in MSL-2 and KIAA1585 include the two cysteine-rich domains described in MSL-2 (Zhou et al 1995;Bashaw and Baker 1995). They are an Nterminal RING finger and a second Cys-rich domain, located C-terminally, which was previously described as a truncated PHD domain (Bashaw and Baker 1995) or as a divergent metallothionein-like domain (Zhou et al 1995). Exhaustive database searches determined that no other available sequence in any species can encode a protein containing those two domains at the same time, a result that strongly suggests that the genes are orthologous.…”