Abstract
BackgroundIn 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.ResultsIn 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.ConclusionsThese 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.
Highlights
In Drosophila melanogaster, dosage compensation is mediated by the action of the dosage compensation complex (DCC)
The final X/2L ratio chosen was 6.8, i. e., words in a region had to be at least 6.8 times relatively more abundant on the X than on an autosome to be selected. This value was chosen because it was the one for whose percentage of X-specific regions that overlapped with DCC binding regions was maximal (Table 1; X-positive regions)
These results demonstrate that most DCC binding regions contain multiple sites related to the [G(CG)N]4 motif that we detected in our original searches, that those sites are relatively close to each other and that they are significantly enriched in most DCC binding regions, with respect to both the rest of the X chromosome and the autosomes
Summary
In Drosophila melanogaster, dosage compensation is mediated by the action of the dosage compensation complex (DCC). In Drosophila, dosage compensation occurs by hypertranscription of the genes of the single X chromosome in males, leading to a level of expression similar to that found for the copies of those same genes located on the two female X chromosomes [1,2,3] This hypertranscription is controlled by a ribonucleoprotein complex, known as Dosage Compensation Complex Immunostaining with antibodies against MSL proteins demonstrated that the DCC complex recognizes hundreds of sites along the male X chromosome [14,15,16,17,18,19,20] How this specificity is achieved is still poorly understood. A sequence motif, containing several GA/TC dinucleotides, has been found to be enriched in high affinity binding sites of the DCC ([29,30]; we will refer to this motif throughout the text as [GA/TC]n)
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