Topic
Dosage compensation
About: Dosage compensation is a research topic. Over the lifetime, 1920 publications have been published within this topic receiving 124589 citations.
Papers published on a yearly basis
Papers
More filters
••
TL;DR: The results uncover new insights into X-dosage in pluripotent stem cells, providing principles of how gene dosage modulates the epigenetic and genetic mechanisms regulating cell identity.
Abstract: During early mammalian development, the two X-chromosomes in female cells are active. Dosage compensation between XX female and XY male cells is then achieved by X-chromosome inactivation in female cells. Reprogramming female mouse somatic cells into induced pluripotent stem cells (iPSCs) leads to X-chromosome reactivation. The extent to which increased X-chromosome dosage (X-dosage) in female iPSCs leads to differences in the molecular and cellular properties of XX and XY iPSCs is still unclear. We show that chromatin accessibility in mouse iPSCs is modulated by X-dosage. Specific sets of transcriptional regulator motifs are enriched in chromatin with increased accessibility in XX or XY iPSCs. We show that the transcriptome, growth and pluripotency exit are also modulated by X-dosage in iPSCs. To understand the mechanisms by which increased X-dosage modulates the molecular and cellular properties of mouse pluripotent stem cells, we used heterozygous deletions of the X-linked gene Dusp9 in XX embryonic stem cells. We show that X-dosage regulates the transcriptome, open chromatin landscape, growth and pluripotency exit largely independently of global DNA methylation. Our results uncover new insights into X-dosage in pluripotent stem cells, providing principles of how gene dosage modulates the epigenetic and genetic mechanisms regulating cell identity.
5 citations
••
TL;DR: In this article, it was suggested that dosage compensation mediates sexual antagonism over X-linked genes, based on the assumption that dose compensation scales phenotypic effects between genes.
Abstract: Recent theory has suggested that dosage compensation mediates sexual antagonism over X-linked genes. This process relies on the assumption that dosage compensation scales phenotypic effects between...
5 citations
••
TL;DR: This work has screened public genomic sequence databases for orthologs and duplicates of 25 genes involved in insect sex determination, identifying patterns of presence and absence and suggesting an inverse association of protein sequence conservation with functional conservation.
Abstract: Abstract The development of dimorphic adult sexes is a critical process for most animals, one that is subject to intense selection. Work in vertebrate and insect model species has revealed that sex determination mechanisms vary widely among animal groups. However, this variation is not uniform, with a limited number of conserved factors. Therefore, sex determination offers an excellent context to consider themes and variations in gene network evolution. Here we review the literature describing sex determination in diverse insects. We have screened public genomic sequence databases for orthologs and duplicates of 25 genes involved in insect sex determination, identifying patterns of presence and absence. These genes and a 3.5 reference set of 43 others were used to infer phylogenies and compared to accepted organismal relationships to examine patterns of congruence and divergence. The function of candidate genes for roles in sex determination (virilizer, female‐lethal‐2‐d, transformer‐2) and sex chromosome dosage compensation (male specific lethal‐1, msl‐2, msl‐3) were tested using RNA interference in the milkweed bug, Oncopeltus fasciatus. None of these candidate genes exhibited conserved roles in these processes. Amidst this variation we wish to highlight the following themes for the evolution of sex determination: (1) Unique features within taxa influence network evolution. (2) Their position in the network influences a component's evolution. Our analyses also suggest an inverse association of protein sequence conservation with functional conservation.
5 citations
••
01 Jan 2011TL;DR: It is proposed that hermaphroditic reproduction is a complex trait, because it requires the independent coordination of different regulatory pathways, one controlling sexual development and the other controlling sperm activation.
Abstract: Self-fertile hermaphrodites have evolved in several independent lineages of nematodes. Surprisingly, both C. elegans and C. briggsae have recruited members of the large family of F-box genes to promote hermaphrodite development. However, C. elegans FOG-2 and C. briggsae SHE-1 have different biochemical functions, and each was created by a unique series of gene duplications. Despite these differences, they share a common target – the transmembrane receptor TRA-2, which plays a central role in the sex-determination pathway. When tra-2 activity is knocked down in the male/female species C. remanei, some of the animals develop as hermaphrodites, but are unable to self-fertilize. This defect is due to the inability of their sperm to auto-activate, since knocking down a second gene that blocks sperm activation leads to self-fertility. Based on these results, we propose that hermaphroditic reproduction is a complex trait, because it requires the independent coordination of different regulatory pathways, one controlling sexual development and the other controlling sperm activation. Further analysis of the evolution of these hermaphrodites should reveal how novel traits first arise during evolution.
4 citations
••
TL;DR: A double-bookmarking system, based on the mutually exclusive relationships of Tsix and RIF1, and KAP1, that coordinates the identification of the active and inactive X chromosomes and initiates a self-sustaining loop that transforms an initially stochastic event into a stably inherited asymmetric X chromosome state.
Abstract: Dosage compensation for the X chromosome-linked genes in female placental mammals is achieved through the random silencing of one of the two X chromosomes. The onset of random X inactivation in mouse embryos and in differentiating embryonic stem cells requires the switch from a symmetric state, where both X chromosomes are equivalent, to an asymmetric state, where the identity of the future inactive and active X chromosomes are assigned. This "choice", initiated by a stochastic event, needs to evolve into a stable and transmissible state. The transition from bi- to mono-allelic expression of the long non-coding RNA Tsix is thought to be one of the initial events breaking the symmetry of the two X chromosomes. Here we show that the asymmetric expression of Tsix triggers in turn the switch of RIF1 association with the Xist promoter from dynamic and symmetric to stable and asymmetric (on the future inactive X). On the future inactive X, RIF1 then plays an essential role in the upregulation of Xist, thus initiating the consolidation and stable transmission of the identity of the inactive X. Tsix-dependent exclusion of RIF1 from the future active X chromosome in turn permits the association of KAP1 with the Xist promoter, thus marking the future active X chromosome. Timely mono-allelic association of KAP1 is important for a stable choice and for X inactivation. We present here a double-bookmarking system, based on the mutually exclusive relationships of Tsix and RIF1, and RIF1 and KAP1. This system coordinates the identification of the active and inactive X chromosomes and initiates a self-sustaining loop that transforms an initially stochastic event into a stably inherited asymmetric X chromosome state.
4 citations