scholarly journals GA-repeats on mammalian X chromosomes support Ohno’s hypothesis of dosage compensation by transcriptional upregulation

2018 ◽  
Author(s):  
Edridge D’Souza ◽  
Elizaveta Hosage ◽  
Kathryn Weinand ◽  
Steve Gisselbrecht ◽  
Vicky Markstein ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transposable Elements ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Binding Sites ◽  
Convergent Evolution ◽  
Fruit Fly ◽  
Dosage Compensation Complex ◽  
X Chromosomes ◽  
Repeat Sequences

ABSTRACTOver 50 years ago, Susumo Ohno proposed that dosage compensation in mammals would require upregulation of gene expression on the single active X chromosome, a mechanism which to date is best understood in the fruit fly Drosophila melanogaster. Here, we report that the GA-repeat sequences that recruit the conserved MSL dosage compensation complex to the Drosophila X chromosome are also enriched across mammalian X chromosomes, providing genomic support for the Ohno hypothesis. We show that mammalian GA-repeats derive in part from transposable elements, suggesting a mechanism whereby unrelated X chromosomes from dipterans to mammals accumulate binding sites for the MSL dosage compensation complex through convergent evolution, driven by their propensity to accumulate transposable elements.

scholarly journals Dosage Compensation Systems

2021 ◽  
pp. 67-89
Author(s):  
Renato Paro ◽  
Ueli Grossniklaus ◽  
Raffaella Santoro ◽  
Anton Wutz
Keyword(s):  
Gene Expression ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Molecular Mechanisms ◽  
Sex Chromosome ◽  
Fruit Fly ◽  
X Chromosomes ◽  
Compensation Systems ◽  
A Cell ◽  
Males And Females

AbstractThis chapter provides an introduction to chromosome-wide dosage compensation systems. We will examine the evolution of dosage compensation, which is thought to be driven by the appearance of differentiated sex chromosomes. In a subset of species with X chromosomal sex determination or XY sex chromosome systems, expression of X-linked genes is regulated by chromosome-wide modifications that equalize gene expression differences between males and females. The molecular mechanisms of X chromosome-wide dosage compensation have been studied in flies, worms, and mammals. Each of these species uses a distinct dosage compensation strategy with a different molecular mechanism. In the wormCaenorhabditis elegans, gene expression on the two X chromosomes of hermaphrodites is reduced to a level that approximates a single X chromosome in males. The fruit flyDrosophila melanogasterachieves dosage compensation by increased transcription of the single X chromosome in males to a level that is similar to the two X chromosomes in females. Lastly, in mammals, one of the two X chromosomes in female cells is transcriptionally inactive and a single X chromosome is transcribed in both sexes. Studies of dosage compensation systems provide insights into how epigenetic regulation controls gene expression and chromatin organization differentially within a cell.

scholarly journals The Caenorhabditis elegans Dosage Compensation Machinery Is Recruited to X Chromosome DNA Attached to an Autosome

Genetics ◽  
2000 ◽  
Vol 156 (4) ◽  
pp. 1603-1621
Author(s):  
Jason D Lieb ◽  
Carlos Ortiz de Solorzano ◽  
Enrique Garcia Rodriguez ◽  
Arthur Jones ◽  
Michael Angelo ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Dna Sequences ◽  
Three Dimensional ◽  
Dosage Compensation Complex ◽  
X Chromosomes ◽  
Cis Acting ◽  
Recognition Elements ◽  
The Right

Abstract The dosage compensation machinery of Caenorhabditis elegans is targeted specifically to the X chromosomes of hermaphrodites (XX) to reduce gene expression by half. Many of the trans-acting factors that direct the dosage compensation machinery to X have been identified, but none of the proposed cis-acting X chromosome-recognition elements needed to recruit dosage compensation components have been found. To study X chromosome recognition, we explored whether portions of an X chromosome attached to an autosome are competent to bind the C. elegans dosage compensation complex (DCC). To do so, we devised a three-dimensional in situ approach that allowed us to compare the volume, position, and number of chromosomal and subchromosomal bodies bound by the dosage compensation machinery in wild-type XX nuclei and XX nuclei carrying an X duplication. The dosage compensation complex was found to associate with a duplication of the right 30% of X, but the complex did not spread onto adjacent autosomal sequences. This result indicates that all the information required to specify X chromosome identity resides on the duplication and that the dosage compensation machinery can localize to a site distinct from the full-length hermaphrodite X chromosome. In contrast, smaller duplications of other regions of X appeared to not support localization of the DCC. In a separate effort to identify cis-acting X recognition elements, we used a computational approach to analyze genomic DNA sequences for the presence of short motifs that were abundant and overrepresented on X relative to autosomes. Fourteen families of X-enriched motifs were discovered and mapped onto the X chromosome.

scholarly journals Two Classes of Dosage Compensation Complex Binding Elements along Caenorhabditis elegans X Chromosomes

2009 ◽  
Vol 29 (8) ◽  
pp. 2023-2031 ◽  
Author(s):  
Timothy A. Blauwkamp ◽  
Gyorgyi Csankovszki
Keyword(s):  
Caenorhabditis Elegans ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Gene Products ◽  
Dosage Compensation Complex ◽  
X Chromosomes ◽  
Linked Gene ◽  
Unknown Mechanism

ABSTRACT Dosage compensation equalizes X-linked gene products between the sexes. In Caenorhabditis elegans, the dosage compensation complex (DCC) binds both X chromosomes in XX animals and halves the transcription from each. The DCC is recruited to the X chromosomes by a number of loci, rex sites, and is thought to spread from these sites by an unknown mechanism to cover the rest of the chromosome. Here we describe a novel class of DCC-binding elements that we propose serve as “way stations” for DCC binding and spreading. Both rex sites and way stations comprise strong foci of DCC binding on the native X chromosome. However, rex sites maintain their ability to bind large amounts of DCC even on X duplications detached from the native X, while way stations do not. These results suggest that two distinct classes of DCC-binding elements facilitate recruitment and spreading of the DCC along the X chromosome.

scholarly journals Chromosome-wide mechanisms to decouple gene expression from gene dose during sex-chromosome evolution

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Bayly S Wheeler ◽  
Erika Anderson ◽  
Christian Frøkjær-Jensen ◽  
Qian Bian ◽  
Erik Jorgensen ◽  
...  
Keyword(s):  
Gene Expression ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Chromosome Evolution ◽  
Sex Chromosome ◽  
Nuclear Periphery ◽  
Single Copy ◽  
Dosage Compensation Complex ◽  
Gene Dose ◽  
Caenorhabditis Elegans Genome

Changes in chromosome number impair fitness by disrupting the balance of gene expression. Here we analyze mechanisms to compensate for changes in gene dose that accompanied the evolution of sex chromosomes from autosomes. Using single-copy transgenes integrated throughout the Caenorhabditis elegans genome, we show that expression of all X-linked transgenes is balanced between XX hermaphrodites and XO males. However, proximity of a dosage compensation complex (DCC) binding site (rex site) is neither necessary to repress X-linked transgenes nor sufficient to repress transgenes on autosomes. Thus, X is broadly permissive for dosage compensation, and the DCC acts via a chromosome-wide mechanism to balance transcription between sexes. In contrast, no analogous X-chromosome-wide mechanism balances transcription between X and autosomes: expression of compensated hermaphrodite X-linked transgenes is half that of autosomal transgenes. Furthermore, our results argue against an X-chromosome dosage compensation model contingent upon rex-directed positioning of X relative to the nuclear periphery.

scholarly journals Induction and inhibition of Drosophila X chromosome gene expression are both impeded by the dosage compensation complex

2021 ◽  
Author(s):  
Richard P Meisel ◽  
Danial Asgari ◽  
Florencia Schlamp ◽  
Robert L Unckless
Keyword(s):  
Gene Expression ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Reproductive Tract ◽  
Sex Chromosome ◽  
Accessory Gland ◽  
Gene Content ◽  
Dosage Compensation Complex ◽  
Specific Expression ◽  
Chromosome Gene

Sex chromosome gene content frequently differs from that of the autosomes, a phenomenon that can be informative of the effects of chromatin environment, sex-specific selection, recombination, and ploidy on genome evolution. For example, the Drosophila X chromosome is depauperate in genes with male-biased expression or limited expression in specific tissues—in particular those expressed in the accessory gland of the male reproductive tract. Multiple hypotheses have been put forth to explain the unique gene content of the X chromosome, including selection against male-beneficial X-linked alleles, expression limits imposed by the haploid dosage of the X in males, and interference by the dosage compensation complex (DCC) on expression in males. Here, we investigate these hypotheses by examining differential gene expression in Drosophila melanogaster following several treatments known to have widespread transcriptomic effects: bacterial infection, viral infection, and abiotic stress. We found that genes that are induced (up-regulated) by these biotic and abiotic treatments are frequently under-represented on the X chromosome, but so are those that are repressed (down-regulated) following treatment. We further show that whether a gene is bound by the DCC in males can largely explain the paucity of both up- and down-regulated genes on the X chromosome. Specifically, genes that are bound by the DCC are unlikely to be up- or down-regulated after treatment. Moreover, genes that are closer to a high-affinity site where the DCC is thought to initiate binding to the X chromosome experience a smaller change in expression following treatment. This relationship, however, could partially be explained by a correlation between differential expression and breadth of expression across tissues. Nonetheless, our results suggest that DCC binding, or the associated chromatin modifications, inhibit both up- and down-regulation of X chromosome gene expression within specific contexts. This effect could explain why the Drosophila X chromosome is depauperate in genes with tissue-specific expression, in addition to the paucity of X-linked genes differentially expressed after biotic or abiotic treatments. We propose multiple possible mechanisms of action for the effect, including a role of Males absent on the first (Mof), a component of the DCC, as a dampener of gene expression variance in both males and females.

scholarly journals Enriched G-quadruplexes on the Drosophila Male X Chromosome Function as Insulators of Dosage Compensation Complex

2019 ◽  
Author(s):  
Sheng-Hu Qian ◽  
Lu Chen ◽  
Zhen-Xia Chen
Keyword(s):  
Y Chromosome ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Binding Sites ◽  
Fine Tuning ◽  
Dosage Compensation Complex ◽  
Evolutionary Trajectory ◽  
Male Specific ◽  
Flanking Regions ◽  
Y Chromosome Degeneration

AbstractThe evolution of sex chromosomes has resulted in half X chromosome dosage in males as females. Dosage compensation, or the two-fold upregulation in males, was thus evolved to balance the gene expression between sexes. However, the step-wise evolutionary trajectory of dosage compensation during Y chromosome degeneration is still unclear. Here, we show that the specific structured elements G-quadruplexes (G4s) are enriched on the X chromosome in Drosophila melanogaster. Meanwhile, on the X chromosome, the G4s are underrepresented on the H4K16 acetylated regions and the binding sites of dosage compensation complex male-specific lethal (MSL) complex. Peaks of G4 density and potential are observed at the flanking regions of MSL binding sites, suggesting G4s act as insulators to precisely up-regulate certain regions in males. Thus, G4s may be involved in the evolution of dosage compensation process through fine-tuning one-dose proto-X chromosome regions around MSL binding sites during the gradual Y chromosome degeneration.One Sentence SummaryG-quadruplexes act as insulators to precisely up-regulate X chromosome in males.

Study of Dosage Compensation in Drosophila

Genetics ◽  
2003 ◽  
Vol 165 (3) ◽  
pp. 1167-1181
Author(s):  
Pei-Wen Chiang ◽  
David M Kurnit
Keyword(s):  
Gene Expression ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Qpcr Assay ◽  
Male And Female ◽  
Multiple Genes ◽  
Chromosomal Changes ◽  
Regulatory Effects

Abstract Using a sensitive RT-QPCR assay, we analyzed the regulatory effects of sex and different dosage compensation mutations in Drosophila. To validate the assay, we showed that regulation for several genes indeed varied with the number of functional copies of that gene. We then confirmed that dosage compensation occurred for most genes we examined in male and female flies. Finally, we examined the effects on regulation of several genes in the MSL pathway, presumed to be involved in sex-dependent determination of regulation. Rather than seeing global alterations of either X chromosomal or autosomal genes, regulation of genes on either the X chromosome or the autosomes could be elevated, depressed, or unaltered between sexes in unpredictable ways for the various MSL mutations. Relative dosage for a given gene between the sexes could vary at different developmental times. Autosomal genes often showed deranged regulatory levels, indicating they were in pathways perturbed by X chromosomal changes. As exemplified by the BR-C locus and its dependent Sgs genes, multiple genes in a given pathway could exhibit coordinate regulatory modulation. The variegated pattern shown for expression of both X chromosomal and autosomal loci underscores the complexity of gene expression so that the phenotype of MSL mutations does not reflect only simple perturbations of genes on the X chromosome.

scholarly journals Absence of X-chromosome dosage compensation in the primordial germ cells of Drosophila embryos

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ryoma Ota ◽  
Makoto Hayashi ◽  
Shumpei Morita ◽  
Hiroki Miura ◽  
Satoru Kobayashi
Keyword(s):  
X Chromosome ◽  
Germ Cells ◽  
Dosage Compensation ◽  
Sex Chromosome ◽  
Primordial Germ Cells ◽  
Histone H4 ◽  
X Chromosomes ◽  
Essential Components ◽  
Msl Complex ◽  
Male Specific

AbstractDosage compensation is a mechanism that equalizes sex chromosome gene expression between the sexes. In Drosophila, individuals with two X chromosomes (XX) become female, whereas males have one X chromosome (XY). In males, dosage compensation of the X chromosome in the soma is achieved by five proteins and two non-coding RNAs, which assemble into the male-specific lethal (MSL) complex to upregulate X-linked genes twofold. By contrast, it remains unclear whether dosage compensation occurs in the germline. To address this issue, we performed transcriptome analysis of male and female primordial germ cells (PGCs). We found that the expression levels of X-linked genes were approximately twofold higher in female PGCs than in male PGCs. Acetylation of lysine residue 16 on histone H4 (H4K16ac), which is catalyzed by the MSL complex, was undetectable in these cells. In male PGCs, hyperactivation of X-linked genes and H4K16ac were induced by overexpression of the essential components of the MSL complex, which were expressed at very low levels in PGCs. Together, these findings indicate that failure of MSL complex formation results in the absence of X-chromosome dosage compensation in male PGCs.

Sign in / Sign up

Export Citation Format

Share Document