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Genes That Implement the Hermaphrodite Mode of Dosage Compensation in Caenorhabditis Elegans

Plenefisch, J. D.; DeLong, L.; Meyer, B. J.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /01/1989 EN
Relevância na Pesquisa
46.8%
We report a genetic characterization of several essential components of the dosage compensation process in Caenorhabditis elegans. Mutations in the genes dpy-26, dpy-27, dpy-28, and the newly identified gene dpy-29 disrupt dosage compensation, resulting in elevated X-linked gene expression in XX animals and an incompletely penetrant maternal-effect XX-specific lethality. These dpy mutations appear to cause XX animals to express each set of X-linked genes at a level appropriate for XO animals. XO dpy animals are essentially wild type. Both the viability and the level of X-linked gene expression in XX animals carrying mutations in two or more dpy genes are the same as in animals carrying only a single mutation, consistent with the view that these genes act together in a single process (dosage compensation). To define a potential time of action for the gene dpy-28 we performed reciprocal temperature-shift experiments with a heat sensitive allele. The temperature-sensitive period for lethality begins 5 hr after fertilization at the 300-cell stage and extends to about 9 hr, a point well beyond the end of cell proliferation. This temperature-sensitive period suggests that dosage compensation is functioning in XX animals by mid-embryogenesis...

Differential Effects of Sex-Lethal Mutations on Dosage Compensation Early in Drosophila Development

Bernstein, M.; Cline, T. W.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /03/1994 EN
Relevância na Pesquisa
46.83%
In response to the primary sex determination signal, X chromosome dose, the Sex-lethal gene controls all aspects of somatic sex determination and differentiation, including X chromosome dosage compensation. Two complementary classes of mutations have been identified that differentially affect Sxl somatic functions: (1) those impairing the ``early' function used to set developmental pathway choice in response to the sex determination signal and (2) those impairing ``late' functions involved in maintaining the pathway choice independent of the initiating signal and/or in directing differentiation. This ``early vs. late' distinction correlates with a switch in promoter utilization from Sxl(Pe) to Sxl(Pm) at the blastoderm stage and a corresponding switch from transcriptional to RNA splicing control. Here we characterize five partial-loss-of-function Sxl alleles to explore a distinction between ``early vs. late' functioning of Sxl in dosage compensation. Assaying for dosage compensation during the blastoderm stage, we find that the earliest phase of the dosage compensation process is controlled by products of the early Sxl promoter, Sxl(Pe). Hence, in addition to triggering the sexual pathway decision of cells, products derived from Sxl(Pe) also control early dosage compensation...

The Caenorhabditis elegans dosage compensation machinery is recruited to X chromosome DNA attached to an autosome.

Lieb, J D; de Solorzano, C O; Rodriguez, E G; Jones, A; Angelo, M; Lockett, S; Meyer, B J
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /12/2000 EN
Relevância na Pesquisa
46.8%
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...

Evolution of dosage compensation in Diptera: the gene maleless implements dosage compensation in Drosophila (Brachycera suborder) but its homolog in Sciara (Nematocera suborder) appears to play no role in dosage compensation.

Ruiz, M F; Esteban, M R; Doñoro, C; Goday, C; Sánchez, L
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /12/2000 EN
Relevância na Pesquisa
46.8%
In Drosophila melanogaster and in Sciara ocellaris dosage compensation occurs by hypertranscription of the single male X chromosome. This article reports the cloning and characterization in S. ocellaris of the gene homologous to maleless (mle) of D. melanogaster, which implements dosage compensation. The Sciara mle gene produces a single transcript, encoding a helicase, which is present in both male and female larvae and adults and in testes and ovaries. Both Sciara and Drosophila MLE proteins are highly conserved. The affinity-purified antibody to D. melanogaster MLE recognizes the S. ocellaris MLE protein. In contrast to Drosophila polytene chromosomes, where MLE is preferentially associated with the male X chromosome, in Sciara MLE is found associated with all chromosomes. Anti-MLE staining of Drosophila postblastoderm male embryos revealed a single nuclear dot, whereas Sciara male and female embryos present multiple intranuclear staining spots. This expression pattern in Sciara is also observed before blastoderm stage, when dosage compensation is not yet set up. The affinity-purified antibodies against D. melanogaster MSL1, MSL3, and MOF proteins involved in dosage compensation also revealed no differences in the staining pattern between the X chromosome and the autosomes in both Sciara males and females. These results lead us to propose that different proteins in Drosophila and Sciara would implement dosage compensation.

Progress and prospects toward our understanding of the evolution of dosage compensation

Vicoso, Beatriz; Bachtrog, Doris
Fonte: Springer Netherlands Publicador: Springer Netherlands
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
46.82%
In many eukaryotic organisms, gender is determined by a pair of heteromorphic sex chromosomes. Degeneration of the non-recombining Y chromosome is a general facet of sex chromosome evolution. Selective pressure to restore expression levels of X-linked genes relative to autosomes accompanies Y-chromosome degeneration, thus driving the evolution of dosage compensation mechanisms. This review focuses on evolutionary aspects of dosage compensation, in light of recent advances in comparative and functional genomics that have substantially increased our understanding of the molecular mechanisms of dosage compensation and how it evolved. We review processes involved in sex chromosome evolution, and discuss the dynamic interaction between Y degeneration and the acquisition of dosage compensation. We compare mechanisms of dosage compensation and the origin of dosage compensation genes between different taxa and comment on sex chromosomes that apparently lack compensation mechanisms. Finally, we discuss how dosage compensation systems can also influence the evolution of well-established sex chromosomes.

Restricting Dosage Compensation Complex Binding to the X Chromosomes by H2A.Z/HTZ-1

Petty, Emily L.; Collette, Karishma S.; Cohen, Alysse J.; Snyder, Martha J.; Csankovszki, Györgyi
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
46.84%
Dosage compensation ensures similar levels of X-linked gene products in males (XY or XO) and females (XX), despite their different numbers of X chromosomes. In mammals, flies, and worms, dosage compensation is mediated by a specialized machinery that localizes to one or both of the X chromosomes in one sex resulting in a change in gene expression from the affected X chromosome(s). In mammals and flies, dosage compensation is associated with specific histone posttranslational modifications and replacement with variant histones. Until now, no specific histone modifications or histone variants have been implicated in Caenorhabditis elegans dosage compensation. Taking a candidate approach, we have looked at specific histone modifications and variants on the C. elegans dosage compensated X chromosomes. Using RNAi-based assays, we show that reducing levels of the histone H2A variant, H2A.Z (HTZ-1 in C. elegans), leads to partial disruption of dosage compensation. By immunofluorescence, we have observed that HTZ-1 is under-represented on the dosage compensated X chromosomes, but not on the non-dosage compensated male X chromosome. We find that reduction of HTZ-1 levels by RNA interference (RNAi) and mutation results in only a very modest change in dosage compensation complex protein levels. However...

Unexpected Role for Dosage Compensation in the Control of Dauer Arrest, Insulin-Like Signaling, and FoxO Transcription Factor Activity in Caenorhabditis elegans

Dumas, Kathleen J.; Delaney, Colin E.; Flibotte, Stephane; Moerman, Donald G.; Csankovszki, Gyorgyi; Hu, Patrick J.
Fonte: Genetics Society of America Publicador: Genetics Society of America
Tipo: Artigo de Revista Científica
Publicado em /07/2013 EN
Relevância na Pesquisa
46.85%
During embryogenesis, an essential process known as dosage compensation is initiated to equalize gene expression from sex chromosomes. Although much is known about how dosage compensation is established, the consequences of modulating the stability of dosage compensation postembryonically are not known. Here we define a role for the Caenorhabditis elegans dosage compensation complex (DCC) in the regulation of DAF-2 insulin-like signaling. In a screen for dauer regulatory genes that control the activity of the FoxO transcription factor DAF-16, we isolated three mutant alleles of dpy-21, which encodes a conserved DCC component. Knockdown of multiple DCC components in hermaphrodite and male animals indicates that the dauer suppression phenotype of dpy-21 mutants is due to a defect in dosage compensation per se. In dpy-21 mutants, expression of several X-linked genes that promote dauer bypass is elevated, including four genes encoding components of the DAF-2 insulin-like pathway that antagonize DAF-16/FoxO activity. Accordingly, dpy-21 mutation reduced the expression of DAF-16/FoxO target genes by promoting the exclusion of DAF-16/FoxO from nuclei. Thus, dosage compensation enhances dauer arrest by repressing X-linked genes that promote reproductive development through the inhibition of DAF-16/FoxO nuclear translocation. This work is the first to establish a specific postembryonic function for dosage compensation in any organism. The influence of dosage compensation on dauer arrest...

The Epigenome of Evolving Drosophila Neo-Sex Chromosomes: Dosage Compensation and Heterochromatin Formation

Zhou, Qi; Ellison, Christopher E.; Kaiser, Vera B.; Alekseyenko, Artyom A.; Gorchakov, Andrey A.; Bachtrog, Doris
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
46.8%
Sex chromosomes originated from autosomes but have evolved a highly specialized chromatin structure. Drosophila Y chromosomes are composed entirely of silent heterochromatin, while male X chromosomes have highly accessible chromatin and are hypertranscribed as a result of dosage compensation. Here, we dissect the molecular mechanisms and functional pressures driving heterochromatin formation and dosage compensation of the recently formed neo-sex chromosomes of Drosophila miranda. We show that the onset of heterochromatin formation on the neo-Y is triggered by an accumulation of repetitive DNA. The neo-X has evolved partial dosage compensation and we find that diverse mutational paths have been utilized to establish several dozen novel binding consensus motifs for the dosage compensation complex on the neo-X, including simple point mutations at pre-binding sites, insertion and deletion mutations, microsatellite expansions, or tandem amplification of weak binding sites. Spreading of these silencing or activating chromatin modifications to adjacent regions results in massive mis-expression of neo-sex linked genes, and little correspondence between functionality of genes and their silencing on the neo-Y or dosage compensation on the neo-X. Intriguingly...

Complete Dosage Compensation and Sex-Biased Gene Expression in the Moth Manduca sexta

Smith, Gilbert; Chen, Yun-Ru; Blissard, Gary W.; Briscoe, Adriana D.
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
Publicado em 19/02/2014 EN
Relevância na Pesquisa
46.86%
Sex chromosome dosage compensation balances homogametic sex chromosome expression with autosomal expression in the heterogametic sex, leading to sex chromosome expression parity between the sexes. If compensation is incomplete, this can lead to expression imbalance and sex-biased gene expression. Recent work has uncovered an intriguing and variable pattern of dosage compensation across species that includes a lack of complete dosage compensation in ZW species compared with XY species. This has led to the hypothesis that ZW species do not require complete compensation or that complete compensation would negatively affect their fitness. To date, only one study, a study of the moth Bombyx mori, has discovered evidence for complete dosage compensation in a ZW species. We examined another moth species, Manduca sexta, using high-throughput sequencing to survey gene expression in the head tissue of males and females. We found dosage compensation to be complete in M. sexta with average expression between the Z chromosome in males and females being equal. When genes expressed at very low levels are removed by filtering, we found that average autosome expression was highly similar to average Z expression, suggesting that the majority of genes in M. sexta are completely dosage compensated. Further...

No Evidence for a Global Male-Specific Lethal Complex-Mediated Dosage Compensation Contribution to the Demasculinization of the Drosophila melanogaster X Chromosome

Vensko, Steven P.; Stone, Eric A.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 05/08/2014 EN
Relevância na Pesquisa
46.8%
In Drosophila melanogaster males, the expression of X-linked genes is regulated by mechanisms that operate on a chromosomal scale. One such mechanism, male-specific lethal complex-dependent X-linked dosage compensation, is thought to broadly enhance the expression of male X-linked genes through two-fold transcriptional upregulation. The evolutionary consequences of this form of dosage compensation are not well understood, particularly with regard to genes more highly expressed in males. It has been observed the X chromosome arrangement of these male-biased genes is non-random, consistent with what one might expect if there is a selective advantage for male-biased genes to avoid dosage compensation. Separately, it has been noted that the male-specific lethal complex and its dosage compensation mechanism appear absent in some male tissues, thus providing a control for the selection hypothesis. Here we utilized publicly available datasets to reassess the arrangement of X-linked male-biased expressed genes after accounting for expression in tissues not dosage compensated by the male-specific lethal complex. Our results do not corroborate previous observations supporting organismal-wide detrimental effects by dosage compensation on X-linked male-biased expressed genes. We instead find no evidence that dosage compensation has played a role in the arrangement of dosage compensated male-biased genes on the X chromosome.

Partial Dosage Compensation in Strepsiptera, a Sister Group of Beetles

Mahajan, Shivani; Bachtrog, Doris
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
Publicado em 18/01/2015 EN
Relevância na Pesquisa
46.82%
Sex chromosomes have evolved independently in many different taxa, and so have mechanisms to compensate for expression differences on sex chromosomes in males and females. Different clades have evolved vastly different ways to achieve dosage compensation, including hypertranscription of the single X in male Drosophila, downregulation of both X’s in XX Caenorhabditis, or inactivation of one X in female mammals. In the flour beetle Tribolium, the X appears hyperexpressed in both sexes, which might represent the first of two steps to evolve dosage compensation along the paths mammals may have taken (i.e., upregulation of X in both sexes, followed by inactivation of one X in females). Here we test for dosage compensation in Strepsiptera, a sister taxon to beetles. We identify sex-linked chromosomes in Xenos vesparum based on genomic analysis of males and females, and show that its sex chromosome consists of two chromosomal arms in Tribolium: The X chromosome that is shared between Tribolium and Strepsiptera, and another chromosome that is autosomal in Tribolium and another distantly related Strepsiptera species, but sex-linked in X. vesparum. We use RNA-seq (RNA sequencing) to show that dosage compensation along the X of X. vesparum is partial and heterogeneous. In particular...

Complete Dosage Compensation in Anopheles stephensi and the Evolution of Sex-Biased Genes in Mosquitoes

Jiang, Xiaofang; Biedler, James K.; Qi, Yumin; Hall, Andrew Brantley; Tu, Zhijian
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
Publicado em 16/06/2015 EN
Relevância na Pesquisa
46.83%
Complete dosage compensation refers to hyperexpression of the entire X or Z chromosome in organisms with heterogametic sex chromosomes (XY male or ZW female) in order to compensate for having only one copy of the X or Z chromosome. Recent analyses suggest that complete dosage compensation, as in Drosophila melanogaster, may not be the norm. There has been no systematic study focusing on dosage compensation in mosquitoes. However, analysis of dosage compensation in Anopheles mosquitoes provides opportunities for evolutionary insights, as the X chromosome of Anopheles and that of its Dipteran relative, D. melanogaster formed independently from the same ancestral chromosome. Furthermore, Culicinae mosquitoes, including the Aedes genus, have homomorphic sex-determining chromosomes, negating the need for dosage compensation. Thus, Culicinae genes provide a rare phylogenetic context to investigate dosage compensation in Anopheles mosquitoes. Here, we performed RNA-seq analysis of male and female samples of the Asian malaria mosquito Anopheles stephensi and the yellow fever mosquito Aedes aegypti. Autosomal and X-linked genes in An. stephensi showed very similar levels of expression in both males and females, indicating complete dosage compensation. The uniformity of average expression levels of autosomal and X-linked genes remained when An. stephensi gene expression was normalized by that of their Ae. aegypti orthologs...

The Epigenome of Evolving Drosophila Neo-Sex Chromosomes: Dosage Compensation and Heterochromatin Formation

Zhou, Qi; Ellison, Christopher E.; Kaiser, Vera B.; Alekseyenko, Artyom A.; Gorchakov, Andrey A.; Bachtrog, Doris
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
EN_US
Relevância na Pesquisa
46.8%
Sex chromosomes originated from autosomes but have evolved a highly specialized chromatin structure. Drosophila Y chromosomes are composed entirely of silent heterochromatin, while male X chromosomes have highly accessible chromatin and are hypertranscribed as a result of dosage compensation. Here, we dissect the molecular mechanisms and functional pressures driving heterochromatin formation and dosage compensation of the recently formed neo-sex chromosomes of Drosophila miranda. We show that the onset of heterochromatin formation on the neo-Y is triggered by an accumulation of repetitive DNA. The neo-X has evolved partial dosage compensation and we find that diverse mutational paths have been utilized to establish several dozen novel binding consensus motifs for the dosage compensation complex on the neo-X, including simple point mutations at pre-binding sites, insertion and deletion mutations, microsatellite expansions, or tandem amplification of weak binding sites. Spreading of these silencing or activating chromatin modifications to adjacent regions results in massive mis-expression of neo-sex linked genes, and little correspondence between functionality of genes and their silencing on the neo-Y or dosage compensation on the neo-X. Intriguingly...

Mechanisms and evolutionary patterns of mammalian and avian dosage compensation

Julien, P.; Brawand, D.; Soumillon, M.; Necsulea, A.; Liechti, A.; Schutz, F.; Daish, T.; Grutzner, F.; Kaessmann, H.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em //2012 EN
Relevância na Pesquisa
66.63%
As a result of sex chromosome differentiation from ancestral autosomes, male mammalian cells only contain one X chromosome. It has long been hypothesized that X-linked gene expression levels have become doubled in males to restore the original transcriptional output, and that the resulting X overexpression in females then drove the evolution of X inactivation (XCI). However, this model has never been directly tested and patterns and mechanisms of dosage compensation across different mammals and birds generally remain little understood. Here we trace the evolution of dosage compensation using extensive transcriptome data from males and females representing all major mammalian lineages and birds. Our analyses suggest that the X has become globally upregulated in marsupials, whereas we do not detect a global upregulation of this chromosome in placental mammals. However, we find that a subset of autosomal genes interacting with X-linked genes have become downregulated in placentals upon the emergence of sex chromosomes. Thus, different driving forces may underlie the evolution of XCI and the highly efficient equilibration of X expression levels between the sexes observed for both of these lineages. In the egg-laying monotremes and birds...

Dosage Compensation of the Drosophila White Gene Requires Both the X Chromosome Environment and Multiple Intragenic Elements

Qian, S.; Pirrotta, V.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/1995 EN
Relevância na Pesquisa
46.86%
The X-linked white gene when transposed to autosomes retains only partial dosage compensation. One copy of the gene in males expresses more than one copy but less than two copies in females. When inserted in ectopic X chromosome sites, the mini-white gene of the CaspeR vector can be fully dosage compensated and can even achieve hyperdosage compensation, meaning that one copy in males gives more expression than two copies in females. As sequences are removed gradually from the 5' end of the gene, we observe a progressive transition from hyperdosage compensation to full dosage compensation to partial dosage compensation. When the deletion reaches -17, the gene can no longer dosage compensate fully even on the X chromosome. A deletion reaching +173, 4 bp preceeding the AUG initiation codon, further reduces dosage compensation both on the X chromosome and on autosomes. This truncated gene can still partially dosage compensate on autosomes, indicating the presence of dosage compensation determinants in the protein coding region. We conclude that full dosage compensation requires an X chromosome environment and that the white gene contains multiple dosage-compensation determinants, some near the promoter and some in the coding region.

The epigenome of evolving Drosophila neo-sex chromosomes: dosage compensation and heterochromatin formation

Zhou, Qi; Ellison, Christopher E.; Kaiser, Vera B.; Alekseyenko, Artyom A.; Gorchakov, Andrey A.; Bachtrog, Doris
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Publicado em 26/09/2013
Relevância na Pesquisa
46.8%
Drosophila Y chromosomes are composed entirely of silent heterochromatin, while male X chromosomes have highly accessible chromatin and are hypertranscribed due to dosage compensation. Here, we dissect the molecular mechanisms and functional pressures driving heterochromatin formation and dosage compensation of the recently formed neo-sex chromosomes of Drosophila miranda. We show that the onset of heterochromatin formation on the neo-Y is triggered by an accumulation of repetitive DNA. The neo-X has evolved partial dosage compensation and we find that diverse mutational paths have been utilized to establish several dozen novel binding consensus motifs for the dosage compensation complex on the neo-X, including simple point mutations at pre-binding sites, insertion and deletion mutations, microsatellite expansions, or tandem amplification of weak binding sites. Spreading of these silencing or activating chromatin modifications to adjacent regions results in massive mis-expression of neo-sex linked genes, and little correspondence between functionality of genes and their silencing on the neo-Y or dosage compensation on the neo-X. Intriguingly, the genomic regions being targeted by the dosage compensation complex on the neo-X and those becoming heterochromatic on the neo-Y show little overlap...

Sex chromosome dosage compensation in Heliconius butterflies: global yet still incomplete?

Walters, James R.; Hardcastle, Thomas J.; Jiggins, Chris D.
Fonte: OUP Publicador: OUP
Tipo: Article; published version
EN
Relevância na Pesquisa
66.82%
This is the final version of the article. It first appeared from Oxford University Press via http://dx.doi.org/10.1093/gbe/evv156.; The evolution of heterogametic sex chromosomes is often?but not always?accompanied by the evolution of dosage compensating mechanisms that mitigate the impact of sex-specific gene dosage on levels of gene expression. One emerging view of this process is that such mechanisms may only evolve in male-heterogametic (XY) species but not in female-heterogametic (ZW) species, which will consequently exhibit ?incomplete? sex chromosome dosage compensation. However, recent results suggest that at least some Lepidoptera (moths and butterflies) may prove to be an exception to this prediction. Studies in bombycoid moths indicate the presence of a chromosome-wide epigenetic mechanism that effectively balances Z chromosome gene expression between the sexes by reducing Z-linked expression in males. In contrast, strong sex chromosome dosage effects without any reduction in male Z-linked expression were previously reported in a pyralid moth, suggesting a lack of any such dosage compensating mechanism. Here we report an analysis of sex chromosome dosage compensation in Heliconius butterflies, sampling multiple individuals for several different adult tissues (head...

Investigation of the roX RNAs and the RNA Helicase MLE in Dosage Compensation in Drosophila melanogaster

Hendricks, Dianne Grayce
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Dissertação Formato: 1502842 bytes; application/pdf
Publicado em //2009 EN_US
Relevância na Pesquisa
66.67%

In Drosophila melanogaster, where males are XY and females are XX, dosage compensation is acheived by approximately two-fold upregulation of transcription of the single male X chromosome. This upregulation is mediated by the dosage compensation complex (DCC), which is assembled in a sequential manner on the male X chromosome and is composed of the two noncoding roX (RNA on the X) RNAs and at least five proteins, including the RNA helicase Maleless (MLE). MLE contains two highly conserved double stranded RNA binding domains (DRBDs) at the N terminus. We investigated the roles of the roX RNAs and MLE helicase through experiments using classical genetic methods to generate and analyze the effects of mutants and mutant transgenes, immunolocalization experiments to study MSL protein and roX RNA to chromosomes. For the first time in vivo, we demonstrate that MLE associates with double stranded RNA in a sequence non-specific manner that is independent of other DCC components. Importantly, we find that the DSRBDs of MLE are essential for dosage compensation but are not required for MLE localization to the male X chromosome. We propose that although the DSRBDs are not essential for ds RNA binding, they may act synergistically with other domains of MLE or other MSLs to associate with RNA in vivo. We propose that a MLE/ roX RNA association involving secondary structure formed by the roX RNAs may be involved in the assembly...

DNA Replication of the Male X Chromosome Is Influenced by the Dosage Compensation Complex in Drosophila melanogaster

DeNapoli, Leyna
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Dissertação
Publicado em //2013
Relevância na Pesquisa
66.67%

Abstract

DNA replication is an integral part of the cell cycle. Every time a cell divides, the entire genome has to be copied once and only once in a timely manner. In order to accomplish this, DNA replication begins at many points throughout the genome. These start sites are called origins of replication, and they are initiated in a temporal manner throughout S phase. How these origins are selected and regulated is poorly understood. Saccharomyces cerevisiae and Schizosaccharomyces pombe have autonomously replicating sequences (ARS) that can replicate plasmids extrachromosomally and function as origins in the genome. Metazoans, however, have shown no evidence of ARS activity.

DNA replication is a multistep process with several opportunities for regulation. Potential origins are marked with the origin recognition complex (ORC), a six subunit complex. In S. cerevisiae, ORC binds to the ARS consensus sequence (ACS), but no sequence specificity is seen in S. pombe or in metazoans. Therefore, factors other than sequence play a role in origin selection.

In G1, the pre-replicative (pre-RC) complex assembles at potential origins. This involves the recruitment of Cdc6 and Cdt1 to ORC, which then recruits MCM2-7 to the origin. In S phase...

Sex and death in birds: A model of dosage compensation that predicts lethality of sex chromosome aneuploids

Graves, Jennifer
Fonte: S Karger AG Publicador: S Karger AG
Tipo: Artigo de Revista Científica
Relevância na Pesquisa
56.44%
Birds show female heterogamety, with ZZ males and ZW females. It is still not clear whether the W is female-determining, or whether two doses of the Z chromosomes are male-determining, or both. This question could easily be settled by the sexual phenotypes of ZZW and ZO birds, in the same way that the sexual phenotypes of XXY and XO showed that the Y is male determining in humans, but that the dosage of an X-borne gene determines sex in Drosophila. However, despite extensive searches, no ZZW or ZO diploid birds have been satisfactorily documented, so we must assume that these genotypes are embryonic lethals. Given that ZW and ZZ are viable and the W contains few genes it is not clear why this should be so. Here I propose that sex chromosome aneuploids are lethal in chicken because, to achieve dosage compensation, a locus on the W chromosome controls the upregulation of genes on the Z in ZW females. ZO birds would therefore have only half the normal dose of Z-linked gene product and ZZW would have twice the amount, both of which would undoubtedly be incompatible with life. Reports of other aneuploids and triploids are also consistent with this hypothesis.