The non-dosage compensated Lsp1α gene of Drosophila melanogaster escapes acetylation by MOF in larval fat body nuclei, but is flanked by two dosage compensated genes

Abstract

<p>Abstract</p> <p>Background</p> <p>In <it>Drosophila melanogaster </it>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 <it>Larval serum protein one </it>α (<it>Lsp1</it>α) gene has long been known to be not dosage compensated. Here we have examined possible explanations for why the <it>Lsp1</it>α gene is not dosage compensated.</p> <p>Results</p> <p>Quantitative RNase protection analysis showed that the genes flanking <it>Lsp1</it>α are expressed equally in males and females and confirmed that <it>Lsp1</it>α is not dosage compensated. Unlike control X-linked genes, <it>Lsp1</it>α was not enriched for H4K16ac in the third instar larval fat body, the tissue in which the gene is actively expressed. X-linked <it>Lsp1α promoter-lacZ </it>reporter transgenes are enriched for H4K16ac in third instar larval fat body. An X-linked reporter gene bracketed by <it>Lsp1</it>α flanking regions was dosage compensated. One of the genes flanking <it>Lsp1</it>α 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 <it>Lsp1</it>α. Phylogenetic analyses of the sequences of the genomes of 12 <it>Drosophila </it>species shows that <it>Lsp1</it>α is only present within the <it>melanogaster </it>subgroup of species.</p> <p>Conclusion</p> <p><it>Lsp1</it>α 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 <it>Lsp1</it>α promoter does not prevent regulation by the MSL complex. The regions flanking <it>Lsp1</it>α do not appear to block access by the MSL complex. <it>Lsp1</it>α appears to have recently evolved within the <it>melanogaster </it>subgroup of <it>Drosophila </it>species. The most likely explanation for why <it>Lsp1</it>α 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.</p