Dosage-sensitive miRNAs trigger modulation of gene expression during genomic imbalance in maize
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PROVIDER: PRJNA782967 | ENA |
REPOSITORIES: ENA
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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
Project description:We examined the impact of both increased and decreased dosage of fifteen distal and one interstitial chromosomal regions via RNA-seq of maize mature leaf tissue to reveal new aspects of genomic imbalance. The results indicate that significant changes in gene expression in aneuploids occur both on the varied chromosome (cis) and the remainder of the genome (trans), with a wider spread of modulation compared with the whole-ploidy series of haploid to tetraploid. In general, cis genes in aneuploids range from a gene-dosage effect to dosage compensation, whereas for trans genes the most common effect is an inverse correlation in that expression is modulated towards the opposite direction of the varied chromosomal dosage, although positive modulations also occur. Furthermore, this analysis revealed the existence of increased and decreased effects in which expression of many genes under genome imbalance are modulated towards the same direction regardless of increased or decreased chromosomal dosage, which is predicted from kinetic considerations of multicomponent molecular interactions. The findings provide novel insights into understanding mechanistic aspects of gene regulation.
2021-02-02 | GSE149186 | GEO
Project description:Gene dosage imbalance in neurodevelopmental disorders
| PRJNA287736 | ENA
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:Aneuploidy is a major source of gene dosage imbalance due to copy number alterations (CNA) and viable human trisomies are model disorders of altered gene expression. We studied gene and allele specific expression (ASE) of 9668 single-cell fibroblasts from T21 discordant twins and from mosaic T21, T18, T13 and T8. We examined 928 single cells with deep scRNAseq. Expected and observed overexpression of trisomic genes in trisomic vs. diploid bulk RNAseq was not detectable in trisomic vs. diploid single cells. Instead, for trisomic genes with low-to-average expression, their altered gene dosage was mainly due to the higher fraction of trisomic cells simultaneously expressing these genes, in agreement with a stochastic 2-state burst-like model of transcription. These results, confirmed in a further analysis of 8740 single fibroblasts, suggest that the specific transcriptional profile of each gene contributes to the phenotypic variability of trisomies. We propose an improved model to understand the effects of CNA and, more generally, of gene regulation on gene dosage imbalance.
2019-10-08 | GSE135500 | GEO
Project description:Gene/genome dosage balance is an essential evolutionary mechanism for organisms to ensure a normal function, but the underlying causes of dosage-imbalance regulation remains poorly understood. Herein, the serial Brassica hybrids/polyploids with different dosages of A and C subgenomes were synthesized to investigate the effects of genome dosages on gene expressions and interaction using RNA-Seq. The expression changes of A- and C-subgenome genes were in accordance with dosage alterations. Dosage-dependent and -independent genes were grouped according to the correlations between dosage variations and gene expressions. Expression levels of dosage-dependent genes were strongly correlated with dosage changes that mainly contributed to dosage effects, while those of dosage-independent genes gave weak correlations with dosage variations that mostly facilitated dosage compensation. More protein–protein interactions were detected for dosage-independent genes than dosage-dependent ones, as predicted by the dosage balance hypothesis. Dosage-dependent genes more likely impacted the expressions by trans effects, whereas dosage-independent genes preferred to play by cis effects. Furthermore, dosage-dependent genes were mainly associated with the basic biological processes to maintain the stability of the growth and development, while dosage-independent genes were more enriched in the stress response related processes to accelerate adaptation. The present comprehensive analysis of gene expression dependent/independent on dosage alterations in Brassica polyploids provided new insights into gene/genome dosage-imbalance regulation of gene expression.
2016-05-25 | GSE81845 | GEO
Project description:Aneuploidy has profound effects on an organism, typically more so than polyploidy, and the basis of this contrast is not fully understood. A dosage series of maize chromosome arm 1L was used to compare relative global gene expression in different types and degrees of aneuploidy to gain insight into how the magnitude of genomic imbalance as well as hypoploidy affect global gene expression. While previously available methods required a selective examination of specific genes, RNA sequencing provides a whole-genome view of gene expression in aneuploids. Most studies of global aneuploid effects have concentrated on trisomics because other types of aneuploids are difficult to produce in most model genetic organisms. The genetic toolkit of maize allows the examination of multiple ploidies and 1-4 doses of chromosome arms. Thus, a detailed examination of expression changes both on the varied chromosome arm and elsewhere in the genome is possible, in both hypoploids and hyperploids, compared with euploid controls. Previous studies observed the inverse trans effect, in which genes not varied in DNA dosage are expressed in a negative relationship to the varied chromosomal region. This response was also the major type of change found globally in this study. It was also found that the effects of aneuploidy are progressive, with more severe aneuploids producing effects of greater magnitude.
2020-02-17 | GSE134936 | GEO
Project description:Single cell transcriptome in aneuploidies reveals mechanisms of gene dosage imbalance
| PRJNA559105 | ENA
Project description:Gene dosage imbalance of heteromorphic sex chromosomes (XY or ZW) exists between the sexes, and with the autosomes. Mammalian X chromosome inactivation was long thought to imply a critical need for dosage compensation in vertebrates. However, mRNA abundance measurements that demonstrated sex chromosome transcripts are neither balanced between the sexes or with autosomes in monotreme mammals or birds brought sex chromosome dosage compensation into question. This study examines transcriptomic and proteomic levels of dosage compensation in platypus and chicken compared to mouse, a model eutherian species. We analyzed mRNA and protein levels in heart and liver tissues of chicken, mouse and platypus.
2024-07-30 | PXD040182 | Pride
Project description:The phenotypic consequences of the addition or subtraction of part of a chromosome is more severe than changing the dosage of the whole genome. By crossing diploid trisomies to a haploid inducer, we identified seventeen distal segmental haploid disomies that cover ~80% of the maize genome. Disomic haploids provide a level of genomic imbalance that is not ordinarily achievable in multicellular eukaryotes, allowing the impact to be stronger and more easily studied. Transcriptome size estimates revealed that a few disomies inversely modulate most of the transcriptome. Based on RNA sequencing, the expression levels of genes located on the varied chromosome arms (cis) in disomies ranged from being proportional to chromosomal dosage (dosage effect) to showing dosage compensation with no expression change with dosage. For genes not located on the varied chromosome arm (trans), an obvious trans-acting effect can be observed, with the majority showing a decreased modulation (inverse effect). The extent of dosage compensation of varied cis genes correlates with the extent of trans inverse effects across the 17 genomic regions studied. The results also have implications for the role of stoichiometry in gene expression, the control of quantitative traits, and the evolution of dosage-sensitive genes.
2021-02-22 | GSE156986 | GEO