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Dosage compensation

About: Dosage compensation is a research topic. Over the lifetime, 1920 publications have been published within this topic receiving 124589 citations.


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Journal ArticleDOI
23 Aug 2013
TL;DR: It is shown that topoisomerase II (Topo II) is enriched on dosage compensated genes, to which it is recruited by association with the MSL complex, in excess of the amount that is present on autosomal genes with similar transcription levels.
Abstract: In Drosophila, dosage compensation is mediated by the MSL complex, which binds numerous sites on the X chromosome in males and enhances the transcriptional rate of a substantial number of X-linked genes. We have determined that topoisomerase II (Topo II) is enriched on dosage compensated genes, to which it is recruited by association with the MSL complex, in excess of the amount that is present on autosomal genes with similar transcription levels. Using a plasmid model, we show that Topo II is required for proper dosage compensation and that compensated chromatin is topologically different from non-compensated chromatin. This difference, which is not the result of the enhanced transcription level due of X-linked genes and which represents a structural modification intrinsic to the DNA of compensated chromatin, requires the function of Topo II. Our results suggest that Topo II is an integral part of the mechanistic basis of dosage compensation.

21 citations

Journal ArticleDOI
TL;DR: Radiation hybrids are a useful tool for high resolution mapping of cis and trans loci capable of affecting gene expression due to copy number change and may serve as a discovery source for novel regulatory loci in noncoding regions of the genome.
Abstract: There is only a limited understanding of the relation between copy number and expression for mammalian genes. We fine mapped cis and trans regulatory loci due to copy number change for essentially all genes using a human-hamster radiation hybrid (RH) panel. These loci are called copy number expression quantitative trait loci (ceQTLs). Unexpected findings from a previous study of a mouse-hamster RH panel were replicated. These findings included decreased expression as a result of increased copy number for 30% of genes and an attenuated relationship between expression and copy number on the X chromosome suggesting an Xist independent form of dosage compensation. In a separate glioblastoma dataset, we found conservation of genes in which dosage was negatively correlated with gene expression. These genes were enriched in signaling and receptor activities. The observation of attenuated X-linked gene expression in response to increased gene number was also replicated in the glioblastoma dataset. Of 523 gene deserts of size > 600 kb in the human RH panel, 325 contained trans ceQTLs with -log10P > 4.1. Recently discovered genes, ultra conserved regions, noncoding RNAs and microRNAs explained only a small fraction of the results, suggesting a substantial portion of gene deserts harbor as yet unidentified functional elements. Radiation hybrids are a useful tool for high resolution mapping of cis and trans loci capable of affecting gene expression due to copy number change. Analysis of two independent radiation hybrid panels show agreement in their findings and may serve as a discovery source for novel regulatory loci in noncoding regions of the genome.

21 citations

Journal ArticleDOI
TL;DR: Comparison of transcription rates in X-chromosomes with the levels of two enzymes coded for by sex-linked genes in males, females, super-females and intersexes revealed that the dosage compensation of the enzyme synthesis is effected at the level of transcription.
Abstract: The intensity of transcription in the polytene X-chromosome of the salivary glands of Drosophila melanogaster has been determined as a function of the ratio of X-chromosomes to autosomes (X:A). Autoradiographic measurements revealed that the single X-chromosome in males (1X2A) incorporates twice as much label as each of the two X-chromosomes in females (2X2A) which confirms the earlier report of Mukherjee and Beermann (1965). The addition of the third autosome set in super-males (1X3A) does not result in an increase of RNA synthesis in the X-chromosomes as compared to normal males (1X2A). In superfemales (3X2A) carrying an extra X-chromosome the transcription in each of the X-chromosomes proceeds with the same rate as in diploid (2X2A) or triploid (3X3A) females. In intersexes (2X3A) the rate of transcription in each of X-chromosomes is intermediate between male and female levels. — The comparison of transcription rates in X-chromosomes with the levels of two enzymes coded for by sex-linked genes in males, females, super-females and intersexes (Faizullin and Gvozdev, 1972, 1973) revealed that the dosage compensation of the enzyme synthesis is effected at the level of transcription.

21 citations

Journal ArticleDOI
TL;DR: In this paper, the authors studied the phenomenon of inactivation in two Y centromeres, having as a control genetically identical active and inactive Y centromres, and concluded that, in the case of the isochromosome, a true deletion of centromeric chromatin is responsible for its stability, whereas in the second case, stability of the dicentric (X;Y) is the result of centromeere chromatin modification.
Abstract: Stable dicentric chromosomes behave as monocentrics because one of the centromeres is inactive. The cause of centromere inactivation is unknown; changes in centromere chromatin conformation and loss of centromeric DNA elements have been proposed as possible mechanisms. We studied the phenomenon of inactivation in two Y centromeres, having as a control genetically identical active Y centromeres. The two cases have the following karyotypes: 45,X/46,X,i(Y)(q12) and 46,XY/ 47,XY,+t(X;Y)(p22.3;p11.3). The analysis of the behaviour of the active and inactive Y chromosome centromeres after Da-Dapi staining, CREST immunofluorescence, and in situ hybridization with centromeric probes leads us to conclude that, in the case of the isochromosome, a true deletion of centromeric chromatin is responsible for its stability, whereas in the second case, stability of the dicentric (X;Y) is the result of centromere chromatin modification.

21 citations

Book ChapterDOI
TL;DR: The mechanism of dosage compensation in Drosophila is discussed in light of recent developments that have brought into question the previous model of dosage Compensation.
Abstract: Epigenetics describes changes in genome function that occur without a change in the DNA sequence. Dosage compensation is a prime example of the regulation of gene expression by an epigenetic mechanism. Dosage compensation has evolved to balance the expression of sex-linked genes in males and females, which possess different numbers of sex chromosomes. However, the genetic sequence of the chromosomes is the same in both sexes. This mechanism therefore needs (1) to function in a sex-specific manner, (2) to target the sex chromosome from amongst the autosomes and (3) to establish and maintain through development a precise, equalised level of gene expression in one sex compared to the other. The process by which dosage compensation is orchestrated has been well characterised in fruit flies and mammals. Although each has evolved a specific dosage-compensation mechanism, these systems share some underlying themes; the molecular components that mediate dosage compensation in both include non-coding RNA molecules, which act as nucleation points for the compensation process. Both systems utilise chromatin-modifying enzymes to remodel large domains of a chromosome. This review will discuss the mechanism of dosage compensation in Drosophila in light of recent developments that have brought into question the previous model of dosage compensation.

21 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202330
202272
202183
202051
201980
201870