A sequence motif enriched in regions bound by the Drosophila dosage compensation complex

Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas (IBV-CSIC), Valencia, Spain.
BMC Genomics (Impact Factor: 3.99). 03/2010; 11(1):169. DOI: 10.1186/1471-2164-11-169
Source: PubMed


In Drosophila melanogaster, dosage compensation is mediated by the action of the dosage compensation complex (DCC). How the DCC recognizes the fly X chromosome is still poorly understood. Characteristic sequence signatures at all DCC binding sites have not hitherto been found.
In this study, we compare the known binding sites of the DCC with oligonucleotide profiles that measure the specificity of the sequences of the D. melanogaster X chromosome. We show that the X chromosome regions bound by the DCC are enriched for a particular type of short, repetitive sequences. Their distribution suggests that these sequences contribute to chromosome recognition, the generation of DCC binding sites and/or the local spreading of the complex. Comparative data indicate that the same sequences may be involved in dosage compensation in other Drosophila species.
These results offer an explanation for the wild-type binding of the DCC along the Drosophila X chromosome, contribute to delineate the forces leading to the establishment of dosage compensation and suggest new experimental approaches to understand the precise biochemical features of the dosage compensation system.

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Available from: Miguel Gallach
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    • "An important caveat of this model is that the GA-rich DNA sequence motif mostly occurs outside the known DCC binding sites and its genome distribution pattern cannot predict X chromosome targeting (Conrad and Akhtar 2011). This strongly suggests that additional DNA sequence elements (Gallach et al. 2010) and/or long-range chromatin context (Conrad and Akhtar 2011) are important for DCC recruitment . On the other hand, several studies seem incompatible with the idea that a recognition element is conserved among Drosophila species. "
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    ABSTRACT: Repetitive DNA are DNA sequences that are repeated multiple times in the genome and normally considered non-functional. Several studies predict that the rapid evolution of chromosome-specific satellites led to hybrid incompatibilities and speciation. Interestingly, in Drosophila, the X and dot chromosomes share a unique and noteworthy property: they are identified by chromosome-specific binding proteins and they are particularly involved in genetic incompatibilities between closely related species. Here, I show that the X and dot chromosomes are overpopulated by certain repetitive elements that undergo recurrent turnover in Drosophila species. The portion of the X and dot chromosomes covered by such satellites is up to 52 times and 44 times higher than in other chromosomes, respectively. In addition, the newly evolved X chromosome in D. pseudoobscura (the chromosomal arm XR) has been invaded by the same satellite that colonized the ancestral X chromosome (chromosomal arm XL), while the autosomal homologs in other species remain mostly devoid of satellites. Contrarily, the Müller element F in D. ananassae, homolog to the dot chromosome in D. melanogaster, has no overrepresented DNA sequences compared to any other chromosome. The biology and evolutionary patterns of the characterized satellites suggest that they provide both chromosomes with some kind of structural identity and are exposed to natural selection. The rapid satellite turnover fits some speciation models and may explain why these two chromosomes are typically involved in hybrid incompatibilities.
    Full-text · Article · May 2014 · Genome Biology and Evolution
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    • "The finding of sequence patterns that are predictive of MSL-binding genes within coding sequences is intriguing, although it has been previously reported [36]. Scoring the sequence words only in the transcribed strand or the correct frame did not improve the coding sequence model, suggesting that the relationships are not attributable to (for instance) specific variations in amino acid composition. "
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    ABSTRACT: In Drosophila melanogaster, the dosage-compensation system that equalizes X-linked gene expression between males and females, thereby assuring that an appropriate balance is maintained between the expression of genes on the X chromosome(s) and the autosomes, is at least partially mediated by the Male-Specific Lethal (MSL) complex. This complex binds to genes with a preference for exons on the male X chromosome with a 3' bias, and it targets most expressed genes on the X chromosome. However, a number of genes are expressed but not targeted by the complex. High affinity sites seem to be responsible for initial recruitment of the complex to the X chromosome, but the targeting to and within individual genes is poorly understood. We have extensively examined X chromosome sequence variation within five types of gene features (promoters, 5' UTRs, coding sequences, introns, 3' UTRs) and intergenic sequences, and assessed its potential involvement in dosage compensation. Presented results show that: the X chromosome has a distinct sequence composition within its gene features; some of the detected variation correlates with genes targeted by the MSL-complex; the insulator protein BEAF-32 preferentially binds upstream of MSL-bound genes; BEAF-32 and MOF co-localizes in promoters; and that bound genes have a distinct sequence composition that shows a 3' bias within coding sequence. Although, many strongly bound genes are close to a high affinity site neither our promoter motif nor our coding sequence signatures show any correlation to HAS. Based on the results presented here, we believe that there are sequences in the promoters and coding sequences of targeted genes that have the potential to direct the secondary spreading of the MSL-complex to nearby genes.
    Full-text · Article · Mar 2012 · BMC Genomics
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    • "This hypertranscription is mediated by acetylation of histone H4 at K16 [5-7] throughout the entire body of transcribed genes hinting that the underlying mechanism may be an increase in the elongation rate of RNA polymerase across X-linked genes [8-11]. The mechanism by which dosage compensation is limited to males is well understood [12-15], but how X-linked genes are distinguished from autosomal genes is only beginning to come into focus [16-19]. "
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    ABSTRACT: The 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. Here, 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. We 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.
    Full-text · Article · Jun 2010 · BMC Biology
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