chromatin component - dosage compensation - basic motif, leucine zipper-like motif, glycine-rich motif protein that directly binds DNA - Msl-1 is thought to form a scaffold to organize the full Male-Specific-Lethal dosage compensation complex, which increases male X chromosome transcription approximately two-fold - functional interplay between MSL1 and CDK7 controls RNA polymerase II Ser5 phosphorylation
Gene model reviewed during 5.51
Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\msl-1 using the Feature Mapper tool.
msl-1 protein is present in male and female larvae but is much less abundant in females.
GBrowse - Visual display of RNA-Seq signalsView Dmel\msl-1 in GBrowse 2
Please Note FlyBase no longer curates genomic clone accessions so this list may not be complete
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.
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.
The msl-1 protein shows a clear bias for binding the exons of genes, rather than binding intergenic regions of the chromosome.
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.
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.
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.
X chromosome proteins associated with dosage compensation in melanogaster are sufficiently conserved to allow significant antibody cross-reaction to D.simulans, D.virilis, D.americana.americana and D.pseudoobscura.pseudoobscura chromosomes. Cross reaction is also observed in the X chromosome and the X2 chromosome (2 copies in females and 1 in males) of D.miranda. These results provide evidence that the male-specific lethal proteins can be acquired on previously unrelated chromosome arms during evolution.
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.
msl-1 requires msl-2 in order to become associated with the X chromosome. msl-1 binding is prevented in females by the Sxl products derived from the activation of the early Sxl promoter. Association of msl-1 with the X chromosome is stable.
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.
Immunostaining of embryonic and larval stages demonstrates that His4, msl-1 and msl-3 are associated with the male X chromosome as early as gastrulation, while mle binding is not detected until the late embryonic/late larval stages.
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 gene products of mle and msl-1 bind to the male X chromosome in an identical pattern. The binding sites of H4Ac16 acetylated form of the His4 product are largely coincident with the mle/msl-1 binding sites. This localisation of H4Ac16 protein is dependent on the dosage compensation regulatory pathway.
The four msl gene products interact to form a multiprotein complex.
Antisera to msl-1 protein label the euchromatic X chromosome through mitosis, but neither the X heterochromatin nor autosomes.
The msl-1 protein is associated with hundreds of sites along the X chromosomes in males, but not females, consistent with its proposed role in increasing the level of X linked transcription in male nuclei.
Mutants are defective for dosage compensation in males. Homozygous male embryos hatch but die as much as twelve 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-11 male embryos are capable of undergoing normal spermatogenesis when transplanted into wild-type hosts.
Mutants show decreased levels of X-linked-enzyme activities (G6PD, 6GPD, FUM) but not autosomally encoded enzymes (ADH, AO, GPDH, IDH) in homozygous msl-11 and msl-12 male larvae when compared with non-msl controls.