Chromosomal duplications increase gene dosage and mRNA level in C. elegans
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PROVIDER: PRJNA816453 | ENA |
REPOSITORIES: ENA
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Project description:Isolation of copy number variations and chromosomal duplications at high frequency in Caenorhabditis elegans suggested that this organism tolerates dosage problems. Here we addressed if this tolerance is due to a genome-wide compensation mechanism acting at the level of mRNA expression. We characterized several chromosomal duplication strains using DNA-seq and analyzed gene expression in two duplication and a fosmid integration strain using mRNA-seq. Our results show that on average, increased gene dosage leads to increased mRNA expression, pointing to a lack of genome-wide dosage compensation. Different genes within the same duplicated region show variable changes in mRNA expression, suggesting feedback regulation of individual genes. Transcriptional repression by somatic dosage compensation and germline silencing contribute to the level of mRNA increase from a large X chromosomal duplication. In sum, our results show a lack of genome-wide dosage compensation mechanism acting at the mRNA level in C. elegans and highlight the role of epigenetic and individual gene regulation contributing to the varied consequences of increased gene dosage.
2022-03-22 | GSE198682 | GEO
Project description:We here describe the first successful construction of a targeted tandem duplication of a large chromosomal segment in Aspergillus oryzae. The targeted tandem chromosomal duplication was achieved by using strains that had 5M-bM-^@M-^YM-NM-^TpyrG upstream of the region targeted for tandem chromosomal duplication and 3M-bM-^@M-^YM-NM-^TpyrG downstream of the target region. Consequently, strains bearing a 210-kb targeted tandem chromosomal duplication near the centromeric region of chromosome 8 and strains bearing a targeted tandem chromosomal duplication of a 700-kb region of chromosome 2 were successfully constructed. The strains bearing the tandem chromosomal duplication were efficiently obtained from the regenerated protoplast of the parental strains. However, the generation of the chromosomal duplication did not depend on the introduction of double-stranded breaks (DSBs) by I-SceI. The chromosomal duplications of these strains were stably maintained after five generations of culture under non-selective conditions. The strains bearing the tandem chromosomal duplication in the 700-kb region of chromosome 2 showed highly increased protease activity in solid-state culture, indicating that the duplication of large chromosomal segments could be a useful new breeding technology and gene analysis method. A. oryzae strain bearing a 210-kb targeted tandem chromosomal duplication, A. oryzae strain bearing a 700-kb targeted tandem chromosomal duplication, and A. oryzae RIB40 (wild type strain), were cultivated in Polypeptone-dextrin medium. After 3 days cultivation, genomic DNAs from the samples were extracted, and array CGH analysis was carried out to confirm the chromosomal duplications in the strains.
2014-06-30 | E-GEOD-57246 | biostudies-arrayexpress
Project description:We here describe the first successful construction of a targeted tandem duplication of a large chromosomal segment in Aspergillus oryzae. The targeted tandem chromosomal duplication was achieved by using strains that had 5’ΔpyrG upstream of the region targeted for tandem chromosomal duplication and 3’ΔpyrG downstream of the target region. Consequently, strains bearing a 210-kb targeted tandem chromosomal duplication near the centromeric region of chromosome 8 and strains bearing a targeted tandem chromosomal duplication of a 700-kb region of chromosome 2 were successfully constructed. The strains bearing the tandem chromosomal duplication were efficiently obtained from the regenerated protoplast of the parental strains. However, the generation of the chromosomal duplication did not depend on the introduction of double-stranded breaks (DSBs) by I-SceI. The chromosomal duplications of these strains were stably maintained after five generations of culture under non-selective conditions. The strains bearing the tandem chromosomal duplication in the 700-kb region of chromosome 2 showed highly increased protease activity in solid-state culture, indicating that the duplication of large chromosomal segments could be a useful new breeding technology and gene analysis method.
2014-06-30 | GSE57246 | GEO
Project description:We report here that duplications of 15 kb or more are common in the genome of the social amoeba Dictyostelium discoideum. Most of the axenic "workhorse" strains Ax2 and Ax3/4 obtained from different laboratories can be expected to carry new duplications. The auxotrophic strains DH1 and JH10 also bear previously unreported duplications. Strain Ax3/4 is known to carry a large duplication on chromosome 2 and the domain boundary of this structure shows evidence of further instability; we find a further variable duplication on chromosome 5. These duplications are lacking in Ax2, which has instead a small duplication on chromosome 1. Stocks of the type isolate NC4 are similarly variable, though we have identified some approximating the assumed ancestral genotype. More recent wild-type isolates are almost without duplications, but we can identify small deletions or regions of high divergence, possibly reflecting responses to local selective pressures. Duplications are scattered through most of the genome, and can be stable enough to reconstruct genealogies spanning decades of the history of the NC4 lineage. The expression level of many duplicated genes is increased with dosage, but for others it appears that some form of dosage compensation occurs.
2008-04-21 | E-TABM-394 | biostudies-arrayexpress
Project description:Chromosomal instability (CIN) is thought to be a source of mutability in human cancer. However, CIN is highly deleterious for the cell, and the resulting aneuploidy induces metabolic stress and compromises cell fitness. Here we utilized the X-chromosome dosage compensation mechanism and changes in X-chromosome number to demonstrate in Drosophila epithelial cells the causal relationship between CIN, aneuploidy, gene dosage imbalance and tumorigenesis. Whereas the harmful effects of CIN can be buffered by resetting the X-chromosome dosage compensation to compensate for changes in X-chromosome number, interfering with the mechanisms of dosage compensation suffices to induce tumorigenesis. In addition, multiple mechanisms buffer the deleterious effects of CIN including DNA-damage repair, activation of the p38 signalling pathway, and induction of cytokine expression to promote compensatory cell proliferation. These data reveal a key role of gene dosage imbalances to CIN-induced programmed cell death and tumorigenesis and the existence of robust compensatory mechanisms.
2016-05-23 | GSE71242 | GEO
Project description:In this study, we achieved translocated chromosomal duplication and triplication of a 1.4-Mb targeted chromosomal region by directly introducing I-SceI meganuclease into A. oryzae protoplast cells. Strains with duplication and triplication of chromosome 2 showed substantial increases in the activity of protease and amylase. Gene dosage effects were enhanced by combining the structural gene and its regulatory gene, indicating that segmental duplications of chromosomes play important phenotypic roles in koji mold strains.
2018-10-23 | GSE120604 | GEO
Project description:We measured gene expression in two isogenic Drosophila lines heterozygous for long deletions. We find that a majority of genes are at least partially compensated at transcription for ½-fold dosage. The degree of compensation does not vary among functional classes of genes. Compensation for deletions is stronger for highly expressed genes than for genes with low expression level. In contrast, the degree of compensation for duplications observed in Gupta et al, 2006, (J. of Biology 5, 3) data for heterozygotes for a duplication is stronger for weakly expressed genes. Thus, transcriptional compensation appears to be based on general regulatory mechanisms that insure high levels of transcription some genes and low transcription levels of other genes, instead of precise maintenance of a particular homeostatic expression level. Given the ubiquity of transcriptional compensation, dominance of wild-type alleles may be at least partially caused by of the regulation at transcription level. Keywords: Genome-wise dosage compensation study Two DrosDel [34] Drosophila melanogaster isogenic lines, Df(3L)ED4475 and Df(3L)ED4543, heterozygous for long deletions on 3L chromosomal branch both maintained against the TM6C balancer were used for microarray experiment. Twenty five adult flies 2-5 days after eclosion were frozen in liquid nitrogen and used for RNA extraction by Trizol method (Invitrogen ®, Carlsbad, CA) in twelve replicates from each line. The two deletion lines served as controls to each other.
2010-06-20 | E-GEOD-14799 | biostudies-arrayexpress
Project description: Not available
| S-EPMC3912847 | biostudies-literature
Project description:We measured gene expression in two isogenic Drosophila lines heterozygous for long deletions. We find that a majority of genes are at least partially compensated at transcription for ½-fold dosage. The degree of compensation does not vary among functional classes of genes. Compensation for deletions is stronger for highly expressed genes than for genes with low expression level. In contrast, the degree of compensation for duplications observed in Gupta et al, 2006, (J. of Biology 5, 3) data for heterozygotes for a duplication is stronger for weakly expressed genes. Thus, transcriptional compensation appears to be based on general regulatory mechanisms that insure high levels of transcription some genes and low transcription levels of other genes, instead of precise maintenance of a particular homeostatic expression level. Given the ubiquity of transcriptional compensation, dominance of wild-type alleles may be at least partially caused by of the regulation at transcription level. Keywords: Genome-wise dosage compensation study
2009-04-03 | GSE14799 | GEO
Project description:Genomic imbalance caused by varying the dosage of individual chromosomes or chromosomal segments (aneuploidy) has more detrimental effects than altering the dosage of complete chromosome sets (ploidy). Previous analysis on RNA-sequencing data of varied dosage of various chromosomal regions in maize (Zea mays) revealed global modulation of gene expression both on the varied chromosome (cis) and the remainder of the genome (trans). Dysregulation of microRNA (miRNA) dosage has been reported to have profound deleterious effects in many species. miRNAs are preferentially retained as duplicates following whole-genome duplication in grass species and are postulated to be dosage-sensitive. However, little is known regarding the role of miRNAs under genomic imbalance. We examined the impact of increased and/or decreased dosage of 1 interstitial and 19 distal chromosomal regions in concert with a whole-genome ploidy series of haploid, diploid, triploid, and tetraploid via small RNA-sequencing of diploid and haploid maize mature leaf tissue to investigate the impact of aneuploidy and polyploidy on expression of miRNAs. In general, cis miRNAs in aneuploids present a predominant gene-dosage effect, whereas trans miRNAs trend toward the inverse level, although other types of responses including dosage compensation, increased effect, and decreased effect also occur. Significant correlations between expression levels of miRNAs and their targets were identified in aneuploids, indicating the regulatory role of miRNAs on gene expression triggered by genomic imbalance. The findings provide novel insights into understanding of gene balance from the aspect of the function of miRNAs.
2022-05-12 | GSE189317 | GEO