Abstract
BackgroundThe Drosophila Male Specific Lethal (MSL) complex contains chromatin modifying enzymes and non-coding roX RNA. It paints the male X at hundreds of bands where it acetylates histone H4 at lysine 16. This epigenetic mark increases expression from the single male X chromosome approximately twofold above what gene-specific factors produce from each female X chromosome. This equalises X-linked gene expression between the sexes. Previous screens for components of dosage compensation relied on a distinctive male-specific lethal phenotype.ResultsHere, we report a new strategy relying upon an unusual male-specific mosaic eye pigmentation phenotype produced when the MSL complex acts upon autosomal roX1 transgenes. Screening the second chromosome identified at least five loci, two of which are previously described components of the MSL complex. We focused our analysis on the modifier alleles of MSL1 and MLE (for 'maleless'). The MSL1 lesions are not simple nulls, but rather alter the PEHE domain that recruits the MSL3 chromodomain and MOF ('males absent on first') histone acetyltransferase subunits to the complex. These mutants are compromised in their ability to recruit MSL3 and MOF, dosage compensate the X, and support long distance spreading from roX1 transgenes. Yet, paradoxically, they were isolated because they somehow increase MSL complex activity immediately around roX1 transgenes in combination with wild-type MSL1 subunits.ConclusionsWe propose that these diverse phenotypes arise from perturbations in assembly of MSL subunits onto nascent roX transcripts. This strategy is a promising alternative route for identifying previously unknown components of the dosage compensation pathway and novel alleles of known MSL proteins.
Highlights
The Drosophila Male Specific Lethal (MSL) complex contains chromatin modifying enzymes and noncoding roX RNA
A genetic screen for dominant modifiers of dosage compensation We carried out a dominant F1 enhancer screen (Figure 1a) on a GMroX1 transgene that carries a wild-type genomic melanogaster roX1 gene on a 4.9 kb EcoRI fragment adjacent to the miniwhite eye pigmentation marker [45] inserted in a YOYO element at 75C in the euchromatic region of the third chromosome
We found that reducing the dose of the known MSL proteins by half in males heterozygous for msl1, msl2, msl3 and mle had no consistent effect on the mosaic eye pattern of males carrying one copy of GMroX1-75C
Summary
The Drosophila Male Specific Lethal (MSL) complex contains chromatin modifying enzymes and noncoding roX RNA It paints the male X at hundreds of bands where it acetylates histone H4 at lysine 16. This epigenetic mark increases expression from the single male X chromosome approximately twofold above what gene-specific factors produce from each female X chromosome. In Drosophila the primary mechanism of dosage compensation is male-specific hypertranscription of most genes along his single X chromosome to match the RNA output from the two X chromosomes found in females [2,3,4] This hypertranscription is mediated by acetylation of histone H4 at K16 [5,6,7] throughout the entire body of transcribed genes hinting. No RNA helicase or non-coding RNA has been linked to the vertebrate MSL complex
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
