Dosage compensation

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

X-Autosome translocations: Cytogenetic characteristics and their consequences

Abstract: To define the principal characteristics of X-autosome translocations, the authors present a study of 105 cases, five of which are personal observations. The autosomal pairs 15, 21, and 22 are affected by t(X-Aut) more often than would be expected. The distribution of breakpoints on the X chromosome does not differ significantly from the expected distribution. The analysis of different patterns of inactivation seems to confirm that the inactivation could occur at random, but would be followed by a cellular selection favoring the better genetic balance. An estimate of the incidence of t(X-Aut) is proposed, based upon the conclusions that only one chromosome is susceptible to translocation in meiosis in both males and females and that all affected men will be sterile, as will be 50% of women.

Condensin controls recruitment of RNA polymerase II to achieve nematode X-chromosome dosage compensation

Abstract: The X-chromosome gene regulatory process called dosage compensation ensures that males (1X) and females (2X) express equal levels of X-chromosome transcripts. The mechanism in Caenorhabditis elegans has been elusive due to improperly annotated transcription start sites (TSSs). Here we define TSSs and the distribution of transcriptionally engaged RNA polymerase II (Pol II) genome-wide in wild-type and dosage-compensation-defective animals to dissect this regulatory mechanism. Our TSS-mapping strategy integrates GRO-seq, which tracks nascent transcription, with a new derivative of this method, called GRO-cap, which recovers nascent RNAs with 5' caps prior to their removal by co-transcriptional processing. Our analyses reveal that promoter-proximal pausing is rare, unlike in other metazoans, and promoters are unexpectedly far upstream from the 5' ends of mature mRNAs. We find that C. elegans equalizes X-chromosome expression between the sexes, to a level equivalent to autosomes, by reducing Pol II recruitment to promoters of hermaphrodite X-linked genes using a chromosome-restructuring condensin complex. DOI:http://dx.doi.org/10.7554/eLife.00808.001.

Expression of Xist in mouse germ cells correlates with X-chromosome inactivation.

Abstract: Mammals compensate for different doses of X-chromosome-linked genes in male (XY) and female (XX) somatic cells by terminally inactivating all but one X chromosome in each cell. A transiently inactive X chromosome is also found in germ cells, specifically in premeiotic oogenic cells and in meiotic and postmeiotic spermatogenic cells. Here we show that the Xist gene, which is a expressed predominantly from the inactive X-chromosome in female somatic cells, is also expressed in germ cells of both sexes, but only at those stages when an inactive X chromosome is present. This suggests support for the putative role of Xist as a regulator of X-chromosome inactivation and suggest a common mechanism for the initiation and/or maintenance of X-chromosome inactivation in all cell types.

Control of Chromosome Inactivation

Abstract: While it is generally believed that eukaryotes must have regulatory mechanisms similar to those of prokaryotes to switch genes on and off as required throughout development (1-5), more clearly established is a different order of genetic regulation, one by which whole chromosomes cr chromosome regions become genetically active and potentially capable of transcription, or seemingly totally genetically inactive and unable to transcribe. The most widely known example is probably that of the mammalian X chromosome (6, 7). Only one X is active in the somatic cells of females, and this system serves as a dosage compensation mechanism, reducing the effective X chromosome dosage in the XX female to that of the XY male. In marsupials, at least in blood cells, the inactive X is always the X derived from the father (8-10), but in eutherian mammals either X may be the inactive one, the choice being made in each cell at an early stage of embryonic development and being fixed in that each descendant cell line follows the original decision and has the same X inactivated. Chromosomal inactivation events are also well documented in species of mealy bugs (11, 12); in Sciara (13, 14), a complex pattern of chromosome loss rather than chromosome inactivation occurs and may represent a more extreme form of the same mecha­ nism. This paper is concerned with this order of genetic regulation and particularly with the behavior of the mammalian X chromosome. Much information is available that establishes the basic concepts of the inactive-X hypothesis beyond all reasonable doubt [for extensive reviews, see Lyon (7,15-19)). In this paper, however, only those aspects of the system that have some bearing on possible control mechanisms are discussed.

Single-cell analysis of transcription kinetics across the cell cycle

Abstract: Transcription is a highly stochastic process. To infer transcription kinetics for a gene-of-interest, researchers commonly compare the distribution of mRNA copy-number to the prediction of a theoretical model. However, the reliability of this procedure is limited because the measured mRNA numbers represent integration over the mRNA lifetime, contribution from multiple gene copies, and mixing of cells from different cell-cycle phases. We address these limitations by simultaneously quantifying nascent and mature mRNA in individual cells, and incorporating cell-cycle effects in the analysis of mRNA statistics. We demonstrate our approach on Oct4 and Nanog in mouse embryonic stem cells. Both genes follow similar two-state kinetics. However, Nanog exhibits slower ON/OFF switching, resulting in increased cell-to-cell variability in mRNA levels. Early in the cell cycle, the two copies of each gene exhibit independent activity. After gene replication, the probability of each gene copy to be active diminishes, resulting in dosage compensation.