Dosage compensation

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

Absence of X-chromosome dosage compensation in the primordial germ cells of Drosophila embryos.

Abstract: Dosage compensation is a mechanism that equalizes sex chromosome gene expression between the sexes. In Drosophila, individuals with two X chromosomes (XX) become female, whereas males have one X chromosome (XY). In males, dosage compensation of the X chromosome in the soma is achieved by five proteins and two non-coding RNAs, which assemble into the male-specific lethal (MSL) complex to upregulate X-linked genes twofold. By contrast, it remains unclear whether dosage compensation occurs in the germline. To address this issue, we performed transcriptome analysis of male and female primordial germ cells (PGCs). We found that the expression levels of X-linked genes were approximately twofold higher in female PGCs than in male PGCs. Acetylation of lysine residue 16 on histone H4 (H4K16ac), which is catalyzed by the MSL complex, was undetectable in these cells. In male PGCs, hyperactivation of X-linked genes and H4K16ac were induced by overexpression of the essential components of the MSL complex, which were expressed at very low levels in PGCs. Together, these findings indicate that failure of MSL complex formation results in the absence of X-chromosome dosage compensation in male PGCs.

Sex-linked gene expression and the emergence of hermaphrodites in Carica papaya

Abstract: Premise One evolutionary path from hermaphroditism to dioecy is via a gynodioecious intermediate. The evolution of dioecy may also coincide with the formation of sex chromosomes that possess sex-determining loci that are physically linked in a region of suppressed recombination. Dioecious papaya (Carica papaya) has an XY chromosome system, where the presence of a Y chromosome determines maleness. However, in cultivation, papaya is gynodioecious, due to the conversion of the male Y chromosome to a hermaphroditic Yh chromosome during its domestication. Methods We investigated gene expression linked to the X, Y, and Yh chromosomes at different floral developmental stages to identify differentially expressed genes that may be involved in the sexual transition of males to hermaphrodites. Results We identified 309 sex-biased genes found on the sex chromosomes, most of which are found in the pseudoautosomal regions. Female (XX) expression in the sex-determining region was almost double that of X-linked expression in males (XY) and hermaphrodites (XYh ), which rules out dosage compensation for most sex-linked genes; although, an analysis of hemizygous X-linked loci found evidence of partial dosage compensation. Furthermore, we identified a candidate gene associated with sex determination and the transition to hermaphroditism, a homolog of the MADS-box protein SHORT VEGETATIVE PHASE. Conclusions We identified a pattern of partial dosage compensation for hemizygous genes located in the papaya sex-determining region. Furthermore, we propose that loss-of-expression of the Y-linked SHORT VEGETATIVE PHASE homolog facilitated the transition from males to hermaphrodites in papaya.

Roles of Long Non-coding RNAs in X-Chromosome Inactivation

Abstract: Organisms in which gender is genetically encoded require a dosage compensation process to equalize sex-linked gene expression between the hetero- and homogametic sexes. In mammals, this dosage compensation process is termed X-chromosome inactivation (XCI). XCI results in the near-complete transcriptional silencing of a single X in XX females, ensuring that only one X per diploid genome remains active. Once stably inactivated, the silent state of the chosen X can be propagated in each cell for the life of the organism, making XCI a paradigm of large-scale epigenetic regulation. Since its discovery more than 50 years ago (Lyon 1961), significant progress has been made toward understanding XCI. In this chapter, we discuss recent advances in the field, with a focus on murine XCI and the essential roles that long, nonprotein coding RNAs play in regulating the process.

flex, an X-linked female-lethal mutation in Drosophila melanogaster controls the expression of Sex-lethal.

Abstract: The Sex-lethal (Sxl) gene is required in Drosophila females for sexual differentiation of the soma, for gem cell differentiation and dosage compensation. We have isolated three new alleles of female-lethal-on-X (flex), an X-linked female-lethal mutation and have characterized its function in sex determination. SXL protein is missing in flex/flex embryos, however transcription from both Sxl(Pe), the early Sxl promoter and Sxl(Pm), the late maintenance promoter, is normal in flex homozygotes. In flex/flex embryos, Sxl mRNA is spliced in the male mode. Analysis of flex germline clones shows that it also functions in oogenesis, but in contrast to Sxl mutants that show an early arrest tumorous phenotype, flex mutant egg chambers develop to stage 10. In flex ovarian clones, Sxl RNA is also spliced in the male form. Hence, flex is a sex-specific regulator of Sxl functioning in both the soma and the germline. Genetic interaction studies show that flex does not enhance female lethality of Sxl loss-of-function alleles but it rescues the male-specific lethality of both of the gain-of-function Sxl mutations, Sxl(M1)and Sxl(M4.) In contrast to mutations in splicing regulators of Sxl, the female lethality of flex is not rescued by either Sxl(M1)or Sxl(M4). Based on these observations, we propose that flex regulates Sxl at a post-splicing stage and regulates either its translation or the stability of the SXL protein.