Dosage compensation

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

Sex, sex chromosomes and gene expression.

Abstract: The X chromosome has fewer testis-specific genes than autosomes in many species. This bias is commonly attributed to X inactivation in spermatogenesis but a recent paper in BMC Biology provides evidence against X inactivation in Drosophila and proposes that somatic tissue- and testis- but not ovary-specific genes tend not to be located on the X chromosome. Here, we discuss possible mechanisms underlying this bias, including sexual antagonism and dosage compensation.

The Influence of Chromosomal Environment on X-Linked Gene Expression in Drosophila melanogaster.

Abstract: Sex chromosomes often differ from autosomes with respect to their gene expression and regulation. In Drosophila melanogaster, X-linked genes are dosage compensated by having their expression upregulated in the male soma, a process mediated by the X-chromosome-specific binding of the dosage compensation complex (DCC). Previous studies of X-linked gene expression found a negative correlation between a gene's male-to-female expression ratio and its distance to the nearest DCC binding site in somatic tissues, including head and brain, which suggests that dosage compensation influences sex-biased gene expression. A limitation of the previous studies, however, was that they focused on endogenous X-linked genes and, thus, could not disentangle the effects of chromosomal position from those of gene-specific regulation. To overcome this limitation, we examined the expression of an exogenous reporter gene inserted at many locations spanning the X chromosome. We observed a negative correlation between the male-to-female expression ratio of the reporter gene and its distance to the nearest DCC binding site in somatic tissues, but not in gonads. A reporter gene's location relative to a DCC binding site had greater influence on its expression than the local regulatory elements of neighboring endogenous genes, suggesting that intra-chromosomal variation in the strength of dosage compensation is a major determinant of sex-biased gene expression. Average levels of sex-biased expression did not differ between head and brain, but there was greater positional effect variation in the brain, which may explain the observed excess of endogenous sex-biased genes located on the X chromosome in this tissue.

Dosage compensation and template organisation in Drosophila: In situ transcriptional analysis of the chromatin template activity of the X and autosomes of D. melanogaster strains trisomic for the left arm of the second and third chromosomes

Abstract: The chromatin template activity of the fixed polytene chromosomes of larval salivary glands of Drosophila melanogaster strains trisomic for the entire left arm of chromosome 2 or chromosome 3 was monitored using 3H-UTP and Escherichia coli RNA polymerase holoenzyme. The three doses of active loci in the trisomic strains were found to synthesize 30%–40% more RNA than the normal double dose of the same region in the wild-type male and female. The higher template activity of the genes on 2L or 3L in the trisomic strains, had no marked effect on the chromatin template activity of the X chromosomes of the male or female. These results suggest that (1) the template activity of an autosomal gene must be viewed as a basal level, comparable to the female X-chromosome and (2) hyperploids for any region of chromosome 2L or 3L have very little or no recognisable influence on X chromosomal organisation.

Bayesian modeling of skewed X inactivation in genetically diverse mice identifies a novel Xce allele associated with copy number changes.

Abstract: Female mammals are functional mosaics of their parental X-linked gene expression due to X chromosome inactivation (XCI). This process inactivates one copy of the X chromosome in each cell during embryogenesis and that state is maintained clonally through mitosis. In mice, the choice of which parental X chromosome remains active is determined by the X chromosome controlling element (Xce), which has been mapped to a 176-kb candidate interval. A series of functional Xce alleles has been characterized or inferred for classical inbred strains based on biased, or skewed, inactivation of the parental X chromosomes in crosses between strains. To further explore the function structure basis and location of the Xce, we measured allele-specific expression of X-linked genes in a large population of F1 females generated from Collaborative Cross (CC) strains. Using published sequence data and applying a Bayesian "Polya urn" model of XCI skew, we report two major findings. First, inter-individual variability in XCI suggests mouse epiblasts contain on average 20-30 cells contributing to brain. Second, CC founder strain NOD/ShiLtJ has a novel and unique functional allele, Xceg, that is the weakest in the Xce allelic series. Despite phylogenetic analysis confirming that NOD/ShiLtJ carries a haplotype almost identical to the well-characterized C57BL/6J (Xceb), we observed unexpected patterns of XCI skewing in females carrying the NOD/ShiLtJ haplotype within the Xce. Copy number variation is common at the Xce locus and we conclude that the observed allelic series is a product of independent and recurring duplications shared between weak Xce alleles.