The non-dosage compensated Lsp1alpha gene of Drosophila melanogaster escapes acetylation by MOF in larval fat body nuclei, but is flanked by two dosage compensated genes.
BACKGROUND
In Drosophila melanogaster dosage compensation of most X-linked genes is mediated by the male-specific lethal (MSL) complex, which includes MOF. MOF acetylates histone H4 at lysine 16 (H4K16ac). The X-linked Larval serum protein one alpha (Lsp1alpha) gene has long been known to be not dosage compensated. Here we have examined possible explanations for why the Lsp1alpha gene is not dosage compensated.


RESULTS
Quantitative RNase protection analysis showed that the genes flanking Lsp1alpha are expressed equally in males and females and confirmed that Lsp1alpha is not dosage compensated. Unlike control X-linked genes, Lsp1alpha was not enriched for H4K16ac in the third instar larval fat body, the tissue in which the gene is actively expressed. X-linked Lsp1alpha promoter-lacZ reporter transgenes are enriched for H4K16ac in third instar larval fat body. An X-linked reporter gene bracketed by Lsp1alpha flanking regions was dosage compensated. One of the genes flanking Lsp1alpha is expressed in the same tissue. This gene shows a modest enrichment for H4K16ac but only at the part of the gene most distant from Lsp1alpha. Phylogenetic analyses of the sequences of the genomes of 12 Drosophila species shows that Lsp1alpha is only present within the melanogaster subgroup of species.


CONCLUSIONS
Lsp1alpha is not modified by the MSL complex but is in a region of the X chromosome that is regulated by the MSL complex. The high activity or tissue-specificity of the Lsp1alpha promoter does not prevent regulation by the MSL complex. The regions flanking Lsp1alpha do not appear to block access by the MSL complex. Lsp1alpha appears to have recently evolved within the melanogaster subgroup of Drosophila species. The most likely explanation for why Lsp1alpha is not dosage compensated is that the gene has not evolved a mechanism to independently recruit the MSL complex, possibly because of its recent evolutionary origin, and because there appears to be a low level of bound MSL complex in a nearby gene that is active in the same tissue.
Weake
Vikki M
VM
Centre for Functional Genomics, Institute of Molecular BioSciences, Massey University, Palmerston North, New Zealand. VMW@stowers-institute.org <VMW@stowers-institute.org>
Scott
Maxwell J
MJ
D000107:Acetylation; D000818:Animals; D030801:Animals, Genetically Modified; D002467:Cell Nucleus / Q000378:metabolism; D004303:Dosage Compensation, Genetic; D029721:Drosophila Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000033:anatomy & histology* / Q000196:embryology / Q000235:genetics*; D019143:Evolution, Molecular; D005216:Fat Body / Q000166:cytology* / Q000378:metabolism; D005260:Female; D050172:Genes, X-Linked; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D019076:Transgenes
D029721:Drosophila Proteins; D006657:Histones; D009687:Nuclear Proteins; D014157:Transcription Factors; C034648:larval serum protein, Drosophila; C082132:msl-1 protein, Drosophila; D051548:Histone Acetyltransferases; C111063:mof protein, Drosophila; D008239:Lysine