MSL2, MSL, kmA
chromatin component - ring finger - metallothionein motif - the key male-specific subunit of the Male-Specific-Lethal dosage compensation complex that induces or stabilizes all other components
Gene model reviewed during 5.52
Component of the male-specific lethal (MSL) histone acetyltransferase complex at least composed of mof, msl-1, msl-2 and msl-3.
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Observed in males but not females.
GBrowse - Visual display of RNA-Seq signalsView Dmel\msl-2 in GBrowse 2
Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see GBrowse for alignment of the cDNAs and ESTs to the gene model.
For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.
The MSL complex does not mediate dosage compensation directly, but rather its activity overrides the high level of histone acetylation and counteracts the potential overexpression of X-linked genes to achieve the proper twofold up-regulation in males.
RNAi screen using dsRNA made from templates generated with primers directed against this gene results in chromosome misalignment on the metaphase spindle when assayed in S2 cells in the presence of Cdc27 dsRNA. This phenotype cannot be observed when the screen is performed without Cdc27 dsRNA.
Sxl protein requires the obligatory cofactor Unr protein for 3'-UTR mediated translational repression of msl-2 in females. Sxl protein recruits Unr protein to the 3' UTR of msl-2 mRNA specifically in female cells.
Gene products of the male specific lethal (msl) group of genes including msl-1, msl-2, msl-3, mle, and mof are associated with all female chromosomes at a low level but are sequestered to the X chromosome in males. There is evidence for the presence of nucleation sites for association of msl proteins with the X chromosome rather than individual gene binding sites.
Gene products of the male specific lethal (msl) group of genes preferentially associate with the male X chromosome and may have a role in dosage compensation. This may be achieved by regulating an inverse dosage effect, which would be maintained on the male X and nullified on the autosomes.
mof colocalises with the MSL complex on the X chromosome: a sequence of binding events results in the formation of the MSL complex on the X chromosome in males and in the targeting of mof to its presumed site of action.
Mutation analysis of the RING finger domain and second cysteine-rich motif confirms that the RING finger is essential for msl-2 function, while suggesting a less stringent requirement for an intact second motif.
Male-specific lethal (MSL) proteins accumulate in a subregion of male nuclei (the X chromosome) beginning at late blastoderm stage. X chromosomal binding of the MSLs is observed throughout embryonic and larval development in both diploid and polytene tissues. His4 colocalises with the MSLs in embryos. Binding of the MSLs is interdependent in diploid cells and is prevented in female embryonic cells by Sxl.
Sex- and chromosome-specific binding of the male-specific lethal (msl) proteins occurs in Drosophilid species spanning 4 genera. msl binding correlates with the evolution of the sex chromosomes.
The products of msl-1, msl-2, mle and msl-3 loci specifically associate with hundreds of sites along the X chromosome in males, but not in females. The binding of each of the four proteins requires the functional products from the other three. 2X3A individuals are mosaic for both Sxl expression and msl-1, msl-2, mle and msl-3 binding to the X chromosome, with a perfect inverse correlation at the cellular level between Sxl expression and msl-1, msl-2, mle and msl-3 X chromosome binding.
msl-2 gene product specifically interacts with the male X chromosome, as do mle, msl-1 and msl-3. msl-2 colocalises with msl-1 and antibodies directed against either msl-2 or msl-1 co-immunoprecipitate both proteins from male nuclear extracts.
Elements needed for dosage compensation are localised to the X chromosome only after blastoderm and msl-dependent dosage compensation is not necessary during the first part of embryogenesis. This suggest the existance of an additional msl-independent dosage compensation mechanism; dosage compensation of run expression at blastoderm is not dependent on male specific lethal genes.
The four msl gene products interact to form a multiprotein complex.
Mutants are defective for dosage compensation in males. Homozygous male embryos hatch but die as much as fourteen days later in larval or prepupal stages; females and heterozygous males survive; phenotype slightly more severe in sons of homozygous than of heterozygous mothers. Viability of two-X individuals that develop as phenotypic males (tra21) or intersexes (dsx1) is unaffected by msl-11, indicating that the one-X condition is required for msl-11 lethality.
Pole cells from msl-21 male embryos are capable of undergoing normal spermatogenesis when transplanted into wild-type hosts.
Few homozygous msl-21 gynandromorphs survive; X0 patches small, with small bristles and mostly confined to abdomen.