Chromosomal basis of dosage compensation in Drosophila

A critical analysis of the puffing activity and transcribing activity patterns of different sites of the X-chromosome of the male and female larval salivary glands of Drosophila hydei has been presented. The results show that within the limitations of the resolving power of the technique and variability inherent in the general chromosomal conditions the puffing activities of the different sites of the X-chromosome are very much alike in the two sexes. Of the 15 puffing sites in the X-chromosome, most of the sites either show good concordance in the two sexes or resemble in their highest class value. Only 4 sites (4CD, 8A, 16C and 20B) show considerable discordance in the activity pattern between male and female. Incorporation of ³H-uridine in the X-chromosome also reveals that there is indeed a reasonable degree of superimposition of the number of silver grains in the X-chromosomal puffs of the two sexes. Whatever disparity that exists between the grain numbers in the two sexes can be explained on the basis of sister-class compensation. These results have been interpreted as evidence in support of the piece-meal mechanism of dosage compensation in Drosophila, operating through hyperactivation in the male.This work has been supported by a grant (No. 10/14/66 G) from the Atomic Energy Establishment, Govt. of India to A.S.M. and a Senior Research Fellowship from the Bhabha Atomic Research Centre, Govt. of India to S.N.C.     

Drosophila dosage compensation

Dosage compensation of X-linked genes is a phenomenon of concerted, chromosome-wide regulation of gene expression underpinned by sustained and tightly regulated histone modifications and chromatin remodeling, coupled with constrains of nuclear architecture. This elaborate process allows the accomplishment of regulated expression of genes on the single male X chromosome to levels comparable to those expressed from the two X chromosomes in females. The ribonucleoprotein Male Specific Lethal (MSL) complex is enriched on the male X chromosome and is intricately involved in this process in Drosophila melanogaster. In this review we discuss the recent advances that highlight the complexity lying behind regulation of gene expression by just two-fold.     

Study of dosage compensation in Drosophila

Using a sensitive RT-QPCR assay, we analyzed the regulatory effects of sex and different dosage compensation mutations in Drosophila. To validate the assay, we showed that regulation for several genes indeed varied with the number of functional copies of that gene. We then confirmed that dosage compensation occurred for most genes we examined in male and female flies. Finally, we examined the effects on regulation of several genes in the MSL pathway, presumed to be involved in sex-dependent determination of regulation. Rather than seeing global alterations of either X chromosomal or autosomal genes, regulation of genes on either the X chromosome or the autosomes could be elevated, depressed, or unaltered between sexes in unpredictable ways for the various MSL mutations. Relative dosage for a given gene between the sexes could vary at different developmental times. Autosomal genes often showed deranged regulatory levels, indicating they were in pathways perturbed by X chromosomal changes. As exemplified by the BR-C locus and its dependent Sgs genes, multiple genes in a given pathway could exhibit coordinate regulatory modulation. The variegated pattern shown for expression of both X chromosomal and autosomal loci underscores the complexity of gene expression so that the phenotype of MSL mutations does not reflect only simple perturbations of genes on the X chromosome.     

A role for siRNA in X-chromosome dosage compensation in Drosophila melanogaster

Sex-chromosome dosage compensation requires selective identification of X chromatin. How this occurs is not fully understood. We show that small interfering RNA (siRNA) mutations enhance the lethality of Drosophila males deficient in X recognition and partially rescue females that inappropriately dosage-compensate. Our findings are consistent with a role for siRNA in selective recognition of X chromatin.