Topic
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: It is concluded that Xist-mediated X chromosome inactivation can occur in the absence ofDNA methylation, arguing that DNA methylation may be required to repress Xist expression for the maintenance of a transcriptionally active Xa.
Abstract: Xist and other X-linked gene expression was examined by fluorescence in situ hybridization in cells of wild type and DNA methyltranferase (Dnmt) mutant embryos and embryonic stem (ES) cells to determine whether demethylation-induced Xist expression leads to inappropriate X chromosome inactivation. In undifferentiated ES cells low-level Xist expression was detected from the single active X chromosome (Xa) in male cells and on both Xa's in female cells. Upon differentiation Xist expression was detected only in female cells, in which Xist RNA colocalized with the entire inactive X chromosome (Xi). Differentiated Dnmt mutant ES cells or cells of mutant postgastrulation embryos showed aberrant patterns of Xist expression: Xist transcripts colocalized with the single X chromosome in male cells and with both X chromosomes in female cells. X-linked gene expression was not detected from chromosomes coated with Xist RNA. These results suggest that ectopic Xist expression, induced by DNA hypomethylation, may lead to the inactivation of X-linked genes. We conclude that Xist-mediated X chromosome inactivation can occur in the absence of DNA methylation, arguing that DNA methylation may be required to repress Xist expression for the maintenance of a transcriptionally active Xa. In differentiated Dnmt mutant ES cells the activation of Xist expression correlated with a dramatic increase in apoptotic bodies, suggesting that Xist-mediated X chromosome inactivation may result in cell death and contribute to the embryonic lethality of the Dnmt mutation.
386 citations
TL;DR: It is demonstrated that, during evolution, the mammalian X chromosome has generated and recruited a disproportionately high number of functional retroposed genes, whereas the autosomes experienced lower gene turnover.
Abstract: Mammalian sex chromosomes have undergone profound changes since evolving from ancestral autosomes. By examining retroposed genes in the human and mouse genomes, we demonstrate that, during evolution, the mammalian X chromosome has generated and recruited a disproportionately high number of functional retroposed genes, whereas the autosomes experienced lower gene turnover. Most autosomal copies originating from X-linked genes exhibited testis-biased expression. Such export is incompatible with mutational bias and is likely driven by natural selection to attain male germline function. However, the excess recruitment is consistent with a combination of both natural selection and mutational bias.
382 citations
TL;DR: P-element-mediated DNA transformation was used to generate transformants carrying segments of DNA from the white locus of D. melanogaster that differed widely in their interactions with the zeste mutation, ranging from greater than normal repression by zeste to insensitivity to the presence of zeste.
372 citations
TL;DR: It is shown that association of MOF with the male X chromosome depends on its interaction with RNA, and MOF specifically binds through its chromodomain to roX2 RNA in vivo.
Abstract: In Drosophila, compensation for the reduced dosage of genes located on the single male X chromosome involves doubling their expression in relation to their counterparts on female X chromosomes1. Dosage compensation is an epigenetic process involving the specific acetylation of histone H4 at lysine 16 by the histone acetyltransferase MOF2,3,4,5. Although MOF is expressed in both sexes, it only associates with the X chromosome in males. Its absence causes male-specific lethality6. MOF is part of a chromosome-associated complex comprising male-specific lethal (MSL) proteins and at least one non-coding roX RNA7. How MOF is integrated into the dosage compensation complex is unknown. Here we show that association of MOF with the male X chromosome depends on its interaction with RNA. MOF specifically binds through its chromodomain to roX2 RNA in vivo. In vitro analyses of the MOF and MSL-3 chromodomains indicate that these chromodomains may function as RNA interaction modules. Their interaction with non-coding RNA may target regulators to specific chromosomal sites.
370 citations
TL;DR: It is argued that the XX embryo is in fact dosage compensated at conception along much of the X chromosome, and proposed that imprinted X inactivation results from inheritance of a pre-inactivated X chromosome from the paternal germ line.
Abstract: In mammals, dosage compensation ensures equal X-chromosome expression between males (XY) and females (XX) by transcriptionally silencing one X chromosome in XX embryos In the prevailing view, the XX zygote inherits two active X chromosomes, one each from the mother and father, and X inactivation does not occur until after implantation Here, we report evidence to the contrary in mice We find that one X chromosome is already silent at zygotic gene activation (2-cell stage) This X chromosome is paternal in origin and exhibits a gradient of silencing Genes close to the X-inactivation centre show the greatest degree of inactivation, whereas more distal genes show variable inactivation and can partially escape silencing After implantation, imprinted silencing in extraembryonic tissues becomes globalized and more complete on a gene-by-gene basis These results argue that the XX embryo is in fact dosage compensated at conception along much of the X chromosome We propose that imprinted X inactivation results from inheritance of a pre-inactivated X chromosome from the paternal germ line
366 citations