Dosage compensation

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

Mechanistic insights into chromosome-wide silencing in X inactivation

Abstract: In mammals, one of the two X chromosomes in female cells is transcriptionally silenced for dosage compensation between the sexes. Chromosome-wide silencing is initiated by the non-coding Xist RNA that accumulates within the inactive X chromosome territory and triggers gene repression and chromatin modifications. Epigenetic changes of the inactive X chromosome in a developmentally regulated manner result in stable gene repression in female somatic cells. X inactivation is a model for understanding the formation of facultative heterochromatin in mammalian development and represents a paradigm for RNA mediated regulation of gene expression. In this review, we summarize the present knowledge of the mechanism of chromosome-wide silencing and give an outlook on future directions.

Mammalian X Chromosome Dosage Compensation: Perspectives From the Germ Line.

Abstract: Sex chromosomes are advantageous to mammals, allowing them to adopt a genetic rather than environmental sex determination system. However, sex chromosome evolution also carries a burden, because it results in an imbalance in gene dosage between females (XX) and males (XY). This imbalance is resolved by X dosage compensation, which comprises both X chromosome inactivation and X chromosome upregulation. X dosage compensation has been well characterized in the soma, but not in the germ line. Germ cells face a special challenge, because genome wide reprogramming erases epigenetic marks responsible for maintaining the X dosage compensated state. Here we explain how evolution has influenced the gene content and germ line specialization of the mammalian sex chromosomes. We discuss new research uncovering unusual X dosage compensation states in germ cells, which we postulate influence sexual dimorphisms in germ line development and cause infertility in individuals with sex chromosome aneuploidy.

The sex-specific region of sex chromosomes in animals and plants

Abstract: Our understanding of the evolution of sex chromosomes has increased greatly in recent years due to a number of molecular evolutionary investigations in divergent sex chromosome systems, and these findings are reshaping theories of sex chromosome evolution. In particular, the dynamics of the sex-determining region (SDR) have been demonstrated by recent findings in ancient and incipient sex chromosomes. Radical changes in genomic structure and gene content in the male specific region of the Y chromosome between human and chimpanzee indicated rapid evolution in the past 6 million years, defying the notion that the pace of evolution in the SDR was fast at early stages but slowed down overtime. The chicken Z and the human X chromosomes appeared to have acquired testis-expressed genes and expanded in intergenic regions. Transposable elements greatly contributed to SDR expansion and aided the trafficking of genes in the SDR and its X or Z counterpart through retrotransposition. Dosage compensation is not a destined consequence of sex chromosomes as once thought. Most X-linked microRNA genes escape silencing and are expressed in testis. Collectively, these findings are challenging many of our preconceived ideas of the evolutionary trajectory and fates of sex chromosomes.

Developmental aspects of X chromosome inactivation in eutherian and metatherian mammals.

Abstract: The single active X principle has served for two decades as a focal point for research on the cyclic activation and inactivation of gene loci. Differences in X chromosome inactivation patterns of eutherian and marsupial mammals provide probes for investigating the mechanisms of the X inactivation process. In eutherian mammals, the X chromosome is inactivated early in meiotic prophase in males and remains inactive throughout the rest of spermatogenesis. During meiosis in females, the inactive X chromosome is activated so that both X chromosomes are active in oocytes. During the early cleavage divisions of female embryos, the paternally derived X is activated. It and the maternally derived X remain active until differentiation begins in early embryogenesis. At that time, the paternally derived X is inactivated in cells that give rise to extraembryonic membranes, whereas a random process determines which X chromosome is inactivated in cells that give rise to the embryo itself. Although less is known about developmental aspects of X inactivation in female marsupials, it is clear that the paternal X is preferentially inactive in postembryonic somatic cells. Furthermore, the paternal X is partially active at some loci in some cell types, indicating that it is not regulated as a single unit. The successful adaptation of a small (80–150 g), fecund marsupial to simple laboratory conditions now enables extensive experimentation on the large number of marsupials at various developmental stages. This capability, coupled with the application of newly developed cellular and molecular techniques to questions about X chromosome inactivation, shows great promise for advancing our understanding of the mechanisms that control the cyclic behavior of X chromosome activity.