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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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TL;DR: P phenotypic characterisation of sexually transformed XO tra-2(eg) hermaphrodites reveals that their fertility is strongly affected by dosage compensation mutations, suggesting that dosage compensation plays a role in normal gametogenesis.
Abstract: Sex determination in the nematode C. elegans is dependent on cell-to-cell communication, which appears to be mediated by the predicted membrane protein TRA-2A and the secreted protein HER-1. In XO males, HER-1 is hypothesised to function as a repressive ligand that inactivates the TRA-2A receptor. In XX animals, HER-1 is absent and TRA-2A promotes hermaphrodite development by negatively regulating the FEM proteins. This paper describes the molecular and genetic characterisation of a novel class of feminising mutations called tra-2(eg), for enhanced gain-of-function. In XX animals, mutant tra-2(eg) activity promotes entirely normal hermaphrodite development. However, the tra-2(eg) mutations generate an XO-specific gain-of-function phenotype, because they transform XO mutants from male into hermaphrodite. Therefore, the tra-2(eg) mutations identify a major regulatory site, which may be the TRA-2A/HER-1 interaction site. All ten tra-2(eg) mutations encode identical missense changes in a predicted extracellular domain of TRA-2A, named the EG site. It is proposed that the tra-2(eg) mutation encodes a TRA-2A protein that functions constitutively in XO animals, because it is defective in HER-1 binding. Phenotypic characterisation of sexually transformed XO tra-2(eg) hermaphrodites reveals that their fertility is strongly affected by dosage compensation mutations, suggesting that dosage compensation plays a role in normal gametogenesis.

37 citations

Journal ArticleDOI
TL;DR: This work systematically examined deficiencies of the left arm of chromosome 2 and characterize gene-by-gene dosage responses that vary from collapsed expression through modest partial dosage compensation to full or even over compensation, suggesting that cases of gene regulation due to altered nuclear architecture are rare.
Abstract: Deletions, commonly referred to as deficiencies by Drosophila geneticists, are valuable tools for mapping genes and for genetic pathway discovery via dose-dependent suppressor and enhancer screens. More recently, it has become clear that deviations from normal gene dosage are associated with multiple disorders in a range of species including humans. While we are beginning to understand some of the transcriptional effects brought about by gene dosage changes and the chromosome rearrangement breakpoints associated with them, much of this work relies on isolated examples. We have systematically examined deficiencies of the left arm of chromosome 2 and characterize gene-by-gene dosage responses that vary from collapsed expression through modest partial dosage compensation to full or even over compensation. We found negligible long-range effects of creating novel chromosome domains at deletion breakpoints, suggesting that cases of gene regulation due to altered nuclear architecture are rare. These rare cases include trans de-repression when deficiencies delete chromatin characterized as repressive in other studies. Generally, effects of breakpoints on expression are promoter proximal (~100bp) or in the gene body. Effects of deficiencies genome-wide are in genes with regulatory relationships to genes within the deleted segments, highlighting the subtle expression network defects in these sensitized genetic backgrounds.

37 citations

Journal ArticleDOI
01 Jan 1984-Genetics
TL;DR: It is proposed that dpy-21 regulates X chromosome expression and may be involved in interpreting X chromosome dose for the developmental decisions of both sex determination and dosage compensation.
Abstract: Recessive mutant alleles at the autosomal dpy-21 locus of C. elegans cause a dumpy phenotype in XX animals but not in XO animals. This dumpy phenotype is characteristic of X chromosome aneuploids with higher than normal X to autosome ratios and is proposed to result from overexpression of X-linked genes. We have isolated a new dpy-21 allele that also causes partial hermaphroditization of XO males, without causing the dumpy phenotype. All dpy-21 alleles show hermaphroditization effects in XO males that carry a duplication of part of the X chromosome and also partially suppress a transformer (tra-1) mutation that converts XX animals into males. Experiments with a set of X chromosome duplications show that the defects of dpy-21 mutants can result from interaction with several different regions of the X chromosome. We propose that dpy-21 regulates X chromosome expression and may be involved in interpreting X chromosome dose for the developmental decisions of both sex determination and dosage compensation.

37 citations

Journal ArticleDOI
TL;DR: The authors developed a scaffolding algorithm and generated chromosome-length assemblies from Hi-C data for studying genome topology in three distantly related Drosophila species, which provides unique insights into genomeTopology evolution.
Abstract: Genome rearrangements that occur during evolution impose major challenges on regulatory mechanisms that rely on three-dimensional genome architecture. Here, we developed a scaffolding algorithm and generated chromosome-length assemblies from Hi-C data for studying genome topology in three distantly related Drosophila species. We observe extensive genome shuffling between these species with one synteny breakpoint after approximately every six genes. A/B compartments, a set of large gene-dense topologically associating domains (TADs), and spatial contacts between high-affinity sites (HAS) located on the X chromosome are maintained over 40 million years, indicating architectural conservation at various hierarchies. Evolutionary conserved genes cluster in the vicinity of HAS, while HAS locations appear evolutionarily flexible, thus uncoupling functional requirement of dosage compensation from individual positions on the linear X chromosome. Therefore, 3D architecture is preserved even in scenarios of thousands of rearrangements highlighting its relevance for essential processes such as dosage compensation of the X chromosome.

37 citations

Journal ArticleDOI
TL;DR: While the majority of iPSC lines maintain an inactive X chromosome, ESC lines tend to silence the expression of XIST and upregulate distal chromosomal regions, which suggest differences in XCI status between most published samples of embryonic stem cells and induced PSCs.

37 citations


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