Interrelationship of RNA interference and transcriptional gene silencing in Drosophila.
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Animals↗
Biomedical subjects
M Pal-Bhadra
Publications and source records attributed to M Pal-Bhadra.
Histone acetylation and gene expression analysis of sex lethal mutants in Drosophila.
The evolution of sex determination mechanisms is often accompanied by reduction in dosage of genes on a whole chromosome. Under these circumstances, negatively acting regulatory genes would tend to double the expression of the genome, which produces compensation of the single-sex chromosome and increases autosomal gene expression. Previous work has suggested that to reduce the autosomal expression to the female level, these dosage effects are modified by a chromatin complex specific to males, which sequesters a histone acetylase to the X. The reduced autosomal histone 4 lysine 16 (H4Lys16) acetylation results in lowered autosomal expression, while the higher acetylation on the X is mitigated by the male-specific lethal complex, preventing overexpression. In this report, we examine how mutations in the principal sex determination gene, Sex lethal (Sxl), impact the H4 acetylation and gene expression on both the X and autosomes. When Sxl expression is missing in females, we find that the sequestration occurs concordantly with reductions in autosomal H4Lys16 acetylation and gene expression on the whole. When Sxl is ectopically expressed in Sxl(M) mutant males, the sequestration is disrupted, leading to an increase in autosomal H4Lys16 acetylation and overall gene expression. In both cases we find relatively little effect upon X chromosomal gene expression.
Acetylation↗
Cosuppression of nonhomologous transgenes in Drosophila involves mutually related endogenous sequences.
Cosuppression refers to the phenomenon in which silencing among dispersed homologous genes occurs. Here we demonstrate that two nonhomologous reciprocal fusion genes, white-Alcohol dehydrogenase (w-Adh) and Adh-w, exhibit cosuppression using the endogenous Adh sequence as an intermediary. Deletion of the endogenous Adh gene eliminates the interaction, while reintroduction of an 8.6 kb Adh fragment restores the silencing. Using truncated Adh constructs, a nontranscribed segment in the Adh regulatory region was found to be one of the sequences required for homology recognition. The silencing interaction is initiated during early development. The silenced transgenes are associated with the Polycomb group complex of chromatin proteins.
Alcohol Dehydrogenase↗
Less from more: cosuppression of transposable elements.
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Animals↗
Role of the male specific lethal (msl) genes in modifying the effects of sex chromosomal dosage in Drosophila.
Immunostaining of chromosomes shows that the male-specific lethal (MSL) proteins are associated with all female chromosomes at a low level but are sequestered to the X chromosome in males. Histone-4 Lys-16 acetylation follows a similar pattern in normal males and females, being higher on the X and lower on the autosomes in males than in females. However, the staining pattern of acetylation and the mof gene product, a putative histone acetylase, in msl mutant males returns to a uniform genome-wide distribution as found in females. Gene expression on the autosomes correlates with the level of histone-4 acetylation. With minor exceptions, the expression levels of X-linked genes are maintained with either an increase or decrease of acetylation, suggesting that the MSL complex renders gene activity unresponsive to H4Lys16 acetylation. Evidence was also found for the presence of nucleation sites for association of the MSL proteins with the X chromosome rather than individual gene binding sequences. We suggest that sequestration of the MSL proteins occurs in males to nullify on the autosomes and maintain on the X, an inverse effect produced by negatively acting dosage-dependent regulatory genes as a consequence of the evolution of the X/Y sex chromosomal system.
Animals↗
Cosuppression in Drosophila: gene silencing of Alcohol dehydrogenase by white-Adh transgenes is Polycomb dependent.
When two to six copies of a white promoter-Alcohol dehydrogenase (Adh) reporter fusion gene are introduced into the genome, the expression is progressively reduced both in larvae and adults rather than the expected gene dosage effect. In addition, multiple transgenes reduce endogenous Adh transcripts, a result that is strongly analogous to "cosuppression" phenomena described in many plant species but which has not been previously observed in animals. Silencing of the Adh gene is not influenced by zeste-dependent transvection but strongly affected by the Polycomb and Polycomblike mutations. Polycomb and polyhomeotic proteins are bound to the chromatin at the sites of the repressed w-Adh transgenes.
Alcohol Dehydrogenase↗
A trans-acting modifier causing extensive overexpression of genes in Drosophila melanogaster.
A modified P element-induced mutation at cytological position 47A11-12 on chromosome 2 of Drosophila melanogaster inversely alters the expression of several genes examined. In addition, the effect is nearly exponential in some developmental stages for five of the eleven genes tested (white, brown, scarlet, rudimentary and vermilion). Interestingly, the exponential overexpression of the transcripts leads to a sexually dimorphic effect, with female levels being greater. The white allele specificity analysis and the lack of response of an Alcohol dehydrogenase promoter-white reporter fusion construct suggest that the 5' regulatory sequences of white are required for the response. Because the cases of extreme overexpression are more prominent in females than males, the locus is termed Ultra female overexpression (Ufo). Ufo revertants have no discernible effect on the transcript levels, indicating that the mutation is responsible for the modulation of the tested genes. Regulatory genes such as Ufo may contribute to the wide fluctuations in gene expression between tissues and stages of development.
ATP-Binding Cassette Transporters↗
A sex-influenced modifier in Drosophila that affects a broad spectrum of target loci including the histone repeats.
A second chromosomal trans-acting modifier, Lightener of white (Low), modulates the phenotypic expression of various alleles of the white eye color gene. This modifier has an unusually broad spectrum of affected genes including white, brown, scarlet and the eye developmental genes, Bar and Lobe. In addition, Low weakly suppresses position effect variegation. Northern blot hybridization with different X and autosomal probes reveals that Low modulates genes of independent expression patterns. Interestingly, many of the modulations of gene expression are developmentally restricted and differ in intensity between the sexes. Low also elevates the expression of the histone tandem repeats in three distinct developmental stages. A deficiency encompassing the histone cluster reduces their transcript levels and significantly alters the expression of some of the tested genes. Thus, Low is a modifier that plays a role in modulating the expression of genes governing various processes including pigment deposition, eye development, chromosomal proteins and position effect variegation.
Alleles↗