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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: This chapter describes the processes coping with sex chromosome genetic imbalance and how ncRNAs underlie dosage compensation mechanisms and influence male-female differences in mammals and discusses how n cRNAs have been tinkered with during therian evolution to adapt XCI mechanistic to species-specific constraints.
Abstract: Genetic sex determination in mammals relies on dimorphic sex chromosomes that confer phenotypic/physiologic differences between males and females. In this heterogametic system, X and Y chromosomes diverged from an ancestral pair of autosomes, creating a genetic disequilibrium between XX females and XY males. Dosage compensation mechanisms alleviate intrinsic gene dosage imbalance, leading to equal expression levels of most X-linked genes in the two sexes. In therian mammals, this is achieved through inactivation of one of the two X chromosomes in females. Failure to undergo X-chromosome inactivation (XCI) results in developmental arrest and death. Although fundamental for survival, a surprising loose conservation in the mechanisms to achieve XCI during development in therian lineage has been, and continues, to be uncovered. XCI involves the concerted action of non-coding RNAs (ncRNAs), including the well-known Xist RNA, and has thus become a classical paradigm to study the mode of action of this particular class of transcripts. In this chapter, we will describe the processes coping with sex chromosome genetic imbalance and how ncRNAs underlie dosage compensation mechanisms and influence male-female differences in mammals. Moreover, we will discuss how ncRNAs have been tinkered with during therian evolution to adapt XCI mechanistic to species-specific constraints.
3 citations
01 Jan 2012
TL;DR: It is reported that mlenapts mutant flies exhibit developmental lethality, decreased fecundity and increased neurodegeneration, and the vital role of Na+ channels in development, longevity and neurodegenersation of flies and their adaptation to temperatures is confirmed.
Abstract: ,istheno-actionpotential temperature sensitive mutation of the maleless (mle) gene.The mle gene encodes an ATP-dependent double-stranded RNAhelicase necessary for X chromosome dosage compensation andmale viability. All mle loss-of-function mutations are male-specificlethal and have normal levels of paralytic (para) encoded Na
3 citations
TL;DR: It is postulate that Top2 and X heterochromatin in Drosophila comprise a novel karyotype-sensing pathway that determines the sensitivity of autosomal heterochromaatin to loss of roX RNA.
Abstract: The eukaryotic genome is assembled into distinct types of chromatin. Gene-rich euchromatin has active chromatin marks, while heterochromatin is gene-poor and enriched for silencing marks. In spite of this, genes native to heterochromatic regions are dependent on their normal environment for full expression. Expression of genes in autosomal heterochromatin is reduced in male flies mutated for the noncoding roX RNAs, but not in females. roX mutations also disrupt silencing of reporter genes in male, but not female, heterochromatin, revealing a sex difference in heterochromatin. We adopted a genetic approach to determine how this difference is regulated, and found no evidence that known X chromosome counting elements, or the sex determination pathway that these control, are involved. This suggested that the sex chromosome karyotype regulates autosomal heterochromatin by a different mechanism. To address this, candidate genes that regulate chromosome organization were examined. In XX flies mutation of Topoisomerase II (Top2), a gene involved in chromatin organization and homolog pairing, made heterochromatic silencing dependent on roX, and thus male-like. Interestingly, Top2 also binds to a large block of pericentromeric satellite repeats (359 bp repeats) that are unique to the X chromosome. Deletion of X heterochromatin also makes autosomal heterochromatin in XX flies dependent on roX and enhances the effect of Top2 mutations, suggesting a combinatorial action. We postulate that Top2 and X heterochromatin in Drosophila comprise a novel karyotype-sensing pathway that determines the sensitivity of autosomal heterochromatin to loss of roX RNA.
3 citations
TL;DR: In this article , a systematic analysis of public sequencing data of both cancerous and normal tissues was conducted, and the authors reported that XIST is somatically activated in a subset of male human cancers across diverse lineages.
Abstract: Expression of the non-coding RNA XIST is essential for initiating X chromosome inactivation (XCI) during early development in female mammals. As the main function of XCI is to enable dosage compensation of chromosome X genes between the sexes, XCI and XIST expression are generally absent in male normal tissues, except in germ cells and in individuals with supernumerary X chromosomes. Via a systematic analysis of public sequencing data of both cancerous and normal tissues, we report that XIST is somatically activated in a subset of male human cancers across diverse lineages. Some of these cancers display hallmarks of XCI, including silencing of gene expression, reduced chromatin accessibility, and increased DNA methylation across chromosome X, suggesting that the developmentally restricted, female-specific program of XCI can be somatically accessed in male cancers.
3 citations
TL;DR: A new study reveals that the concept of spreading also holds true for establishing domains of active chromatin for spreading of repressor proteins along large chromosomal domains.
Abstract: The formation of heterochromatin involves spreading of repressor proteins along large chromosomal domains. A new study reveals that the concept of spreading also holds true for establishing domains of active chromatin. More specifically, spreading of the Drosophila melanogaster male-specific lethal (MSL) activator complex, which is required for dosage compensation on the X chromosome, involves interaction between the MSL3 chromodomain and histone H3 methylated at lysine 36.
3 citations