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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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Book ChapterDOI
TL;DR: This review will summarize current knowledge of the function of the noncoding roX genes in this process in Drosophila and identify an autosomal function for the roX RNAs, raising intriguing questions about the origin of the modern dosage compensation system in flies.
Abstract: Organisms with dimorphic sex chromosomes suffer a potentially lethal imbalance in gene expression in one sex. Addressing this fundamental problem can be considered the first, and most essential, aspect of sexual differentiation. In the model organisms Drosophila, Caenorhabditis elegans, and mouse, expression from X-linked genes is modulated by selective recruitment of chromatin-modifying complexes to X chromatin. In both flies and mammals, large noncoding RNAs have a central role in recruitment and activity of these complexes. This review will summarize current knowledge of the function of the noncoding roX genes in this process in Drosophila. Identification of an autosomal function for the roX RNAs raises intriguing questions about the origin of the modern dosage compensation system in flies.

9 citations

Journal ArticleDOI
TL;DR: It is reported that Eed, along with its binding partner Enx1, transiently associates with the inactive X chromosome (Xi) and likely contributes to the epigenetic signature and long-term stability of the Xi heterochromatin.

9 citations

Journal ArticleDOI
TL;DR: The functional status of the X chromosome in Acheta domesticus has been analyzed at the whole chromosome level on the basis of 3H-thymidine autoradiography, 5-BrdU/AO fluorescence microscopy, in vivo 5-brdU incorporation and induced aberrations.
Abstract: The functional status of the X chromosome in Acheta domesticus has been analysed at the whole chromosome level on the basis of (1) 3H-thymidine autoradiography, (2) 5-BrdU/AO fluorescence microscopy, (3) in vivo 5-BrdU incorporation and (4) 3H-UdR induced aberrations. The rationale of these techniques in relation to the functional aspect of the X chromosome is that the inactive X chromosome would (1) show asynchrony in DNA synthesis, (2) show differential fluorescence, (3) respond differentially to in vivo 5-BrdU treatment and (4) the active X chromosome would show aberrations when treated with 3H-Uridine. From the results, it appears that the X chromosomes in both male (XO) and female (XX) somatic cells of Acheta are euchromatic (active). Further, the single X in the male is transcriptionally as active as the two X chromosomes in the female. In other words, the single X in the male is hyperactive when compared with the single X in the female. From this it is inferred that the male X chromosome is differentially regulated in order to bring about an equalization of it's gene product(S) to that produced by both Xs in the female. Drosophila melanogaster has a comparable system of dosage compensation. Thus, Acheta is yet another insect showing evidence for an X chromosome regulatory mechanism of dosage compensation. Additionally, it is surmised that sex determination in Acheta is based on an autosomes/X chromosome balance mechanism.

9 citations

Journal ArticleDOI
TL;DR: In this paper, the authors defined sites and kinetics of DCC recruitment on the X chromosome in high spatial resolution at different developmental time points and provided important and unexpected insights into the process of dosage compensation, challenging and helping to redefine current models.
Abstract: Dosage compensation solves the chromosomal imbalance that is a result of sexual determination by sex chromosomes. It equalizes gene expression between the homogametic (XX) and heterogametic (XY) sexes and thus needs to selectively modify expression from the X chromosome in a sex-specific manner without affecting transcription on the autosomes. Various strategies have evolved in different organisms to achieve this balance, and their study has contributed significantly to our understanding of transcriptional gene regulation of whole chromosomes and established several paradigms of epigenetic control (Lucchesi 1998; Stuckenholz et al. 1999; Akhtar 2003). In mammals, dosage compensation is accomplished by inactivating one copy of the X chromosome in females via an epigenetic process of allele-specific modification of chromatin and DNA. In Drosophila, dosage compensation is achieved not by repression but by increasing the transcription specifically on the single male X chromosome (Hamada et al. 2005; Straub et al. 2005). Genetic screens for male-specific lethality (MSL) identified five protein-coding genes that are required for dosage compensation: Msl 1-3, male absent on the first (mof), and maleless (mle). Subsequent biochemical characterizations suggested that these proteins, together with two noncoding RNAs (roX1 and roX2), form what has been termed the dosage compensation complex (DCC) (for review, see Bashaw and Baker 1996; Gilfillan et al. 2004). Complex formation only occurs in males, as translation of the MSL-2 protein is inhibited in females. A first evidence for chromatin as a target in dosage compensation came from the observation of higher levels of histone H4K16 acetylation on the hyperactivated X detected by immunostaining (Turner et al. 1992). One of the msl genes, MOF, is a histone acetyl-transferase (HAT) that acetylates H4 at Lys 16 and is able to cause derepression of chromatinized templates in vitro and in vivo (Akhtar and Becker 2000). Thus, it appears that the HAT activity of MOF plays an important part in the mechanisms that lead to hyperactivation of the male X (Smith et al. 2000). A large body of work in different systems established that histone hyperacetylation correlates with gene activation, making this a feasible model (Wade et al. 1997). Yet how does the recruitment of a HAT activity that acetylates a single lysine on H4 result in a precise twofold up-regulation of mRNA? As histone acetylation is involved in promoter activation, it has been assumed that DCC is recruited to promoters of genes at the X chromosome, but is this really the site of action in vivo? Are individual genes targeted by DCC, or are large chromosomal regions covered? Equally as important, how does this process ensure regulation of X-linked genes that are dynamically expressed during development? Is compensation set up early in development for all genes independent of their subsequent activity, or is the DCC relocated dynamically to any activated gene? Many of these questions can be approached by defining sites and kinetics of DCC recruitment on the X chromosome in high spatial resolution at different developmental time points. No less than three reports in this issue of Genes & Development provide such chromosome-wide analysis of several MSL proteins. Together they provide important and unexpected insights into the process of dosage compensation, challenging and helping to redefine current models (Alekseyenko et al. 2006; Gilfillan et al. 2006; Legube et al. 2006).

9 citations


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