Kovalchuk, Igor

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https://opus.uleth.ca/handle/10133/3488

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Browsing Kovalchuk, Igor by Author "Ilnytskyy, Yaroslav"

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    The elucidation of stress memory inheritance in Brassica rapa plants
    (Frontiers Media, 2015) Bilichak, Andriy; Ilnytskyy, Yaroslav; Woycicki, Rafal; Kepeshchuk, Nina; Fogen, Dawson; Kovalchuk, Igor
    Plants are able to maintain the memory of stress exposure throughout their ontogenesis and faithfully propagate it into the next generation. Recent evidence argues for the epigenetic nature of this phenomenon. Small RNAs (smRNAs) are one of the vital epigenetic factors because they can both affect gene expression at the place of their generation and maintain non-cell-autonomous gene regulation. Here, we have made an attempt to decipher the contribution of smRNAs to the heat-shock-induced transgenerational inheritance in Brassica rapa plants using sequencing technology. To do this, we have generated comprehensive profiles of a transcriptome and a small RNAome (smRNAome) from somatic and reproductive tissues of stressed plants and their untreated progeny. We have demonstrated that the highest tissue-specific alterations in the transcriptome and smRNAome profile are detected in tissues that were not directly exposed to stress, namely, in the endosperm and pollen. Importantly, we have revealed that the progeny of stressed plants exhibit the highest fluctuations at the smRNAome level but not at the transcriptome level. Additionally,we have uncovered the existence of heat-inducible and transgenerationally transmitted tRNA-derived small RNA fragments in plants. Finally,we suggest that miR168 and braAGO1 are involved in the stress-induced transgenerational inheritance in plants
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    Environmental intervention as a therapy for adverse programming by ancestral stress
    (Nature Research, 2016) McCreary, J. Keiko; Erickson, Zachary T.; Hao, XongXin; Ilnytskyy, Yaroslav; Kovalchuk, Igor; Metz, Gerlinde A. S.
    Ancestral stress can program stress sensitivity and health trajectories across multiple generations. While ancestral stress is uncontrollable to the filial generations, it is critical to identify therapies that overcome transgenerational programming. Here we report that prenatal stress in rats generates a transgenerationally heritable endocrine and epigenetic footprint and elevated stress sensitivity which can be alleviated by beneficial experiences in later life. Ancestral stress led to downregulated glucocorticoid receptor and prefrontal cortex neuronal densities along with precocious development of anxiety-like behaviours. Environmental enrichment (EE) during adolescence mitigated endocrine and neuronal markers of stress and improved miR-182 expression linked to brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) regulation in stressed lineages. Thus, EE may serve as a powerful intervention for adverse transgenerational programming through microRNA-mediated regulation of BDNF and NT-3 pathways. The identification of microRNAs that mediate the actions of EE highlights new therapeutic strategies for mental health conditions and psychiatric disease.
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    Genomic and epigenomic changes in the progeny of cold-stressed Arabidopsis thaliana plants
    (MDPI, 2024) Rahman, Ashif; Yadav, Narendra Singh; Byeon, Boseon; Ilnytskyy, Yaroslav; Kovalchuk, Igor
    Plants are continuously exposed to various environmental stresses. Because they can not escape stress, they have to develop mechanisms of remembering stress exposures somatically and passing it to the progeny. We studied the Arabidopsis thaliana ecotype Columbia plants exposed to cold stress for 25 continuous generations. Our study revealed that multigenerational exposure to cold stress resulted in the changes in the genome and epigenome (DNA methylation) across generations. Main changes in the progeny were due to the high frequency of genetic mutations rather than epigenetic changes; the difference was primarily in single nucleotide substitutions and deletions. The progeny of cold-stressed plants exhibited the higher rate of missense non-synonymous mutations as compared to the progeny of control plants. At the same time, epigenetic changes were more common in the CHG (C = cytosine, H = cytosine, adenine or thymine, G = guanine) and CHH contexts and favored hypomethylation. There was an increase in the frequency of C to T (thymine) transitions at the CHH positions in the progeny of cold stressed plants; because this type of mutations is often due to the deamination of the methylated cytosines, it can be hypothesized that environment-induced changes in methylation contribute to mutagenesis and may be to microevolution processes and that RNA-dependent DNA methylation plays a crucial role. Our work supports the existence of heritable stress response in plants and demonstrates that genetic changes prevail.
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    Genomic and epigenomic responses to chronic stress involve miRNA-mediated programming
    (Public Library of Science, 2012) Babenko, Olena M.; Golubov, Andrey; Ilnytskyy, Yaroslav; Kovalchuk, Igor; Metz, Gerlinde A. S.
    Stress represents a critical influence on motor system function and has been shown to impair movement performance. We hypothesized that stress-induced motor impairments are due to brain-specific changes in miRNA and protein-encoding gene expression. Here we show a causal link between stress-induced motor impairment and associated genetic and epigenetic responses in relevant central motor areas in a rat model. Exposure to two weeks of mild restraint stress altered the expression of 39 genes and nine miRNAs in the cerebellum. In line with persistent behavioural impairments, some changes in gene and miRNA expression were resistant to recovery from stress. Interestingly, stress up-regulated the expression of Adipoq and prolactin receptor mRNAs in the cerebellum. Stress also altered the expression of Prlr, miR-186, and miR-709 in hippocampus and prefrontal cortex. In addition, our findings demonstrate that miR-186 targets the gene Eps15. Furthermore, we found an age-dependent increase in EphrinB3 and GabaA4 receptors. These data show that even mild stress results in substantial genomic and epigenomic changes involving miRNA expression and associated gene targets in the motor system. These findings suggest a central role of miRNA-regulated gene expression in the stress response and in associated neurological function.
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    Lifetime stress cumulatively programs brain transcriptome and impedes stroke recovery: benefit of sensory stimulation
    (Public Library of Science, 2014) Zucchi, Fabiola C. R.; Yao, Youli; Ilnytskyy, Yaroslav; Robbins, Jerrah C.; Soltanpour, Nasrin; Kovalchuk, Igor; Kovalchuk, Olga; Metz, Gerlinde A. S.
    Prenatal stress (PS) represents a critical variable affecting lifetime health trajectories, metabolic and vascular functions. Beneficial experiences may attenuate the effects of PS and its programming of health outcomes in later life. Here we investigated in a rat model (1) if PS modulates recovery following cortical ischemia in adulthood; (2) if a second hit by adult stress (AS) exaggerates stress responses and ischemic damage; and (3) if tactile stimulation (TS) attenuates the cumulative effects of PS and AS. Prenatally stressed and non-stressed adult male rats underwent focal ischemic motor cortex lesion and were tested in skilled reaching and skilled walking tasks. Two groups of rats experienced recurrent restraint stress in adulthood and one of these groups also underwent daily TS therapy. Animals that experienced both PS and AS displayed the most severe motor disabilities after lesion. By contrast, TS promoted recovery from ischemic lesion and reduced hypothalamic-pituitary-adrenal axis activity. The data also showed that cumulative effects of adverse and beneficial lifespan experiences interact with disease outcomes and brain plasticity through the modulation of gene expression. Microarray analysis of the lesion motor cortex revealed that cumulative PS and AS interact with genes related to growth factors and transcription factors, which were not affected by PS or lesion alone. TS in PS+AS animals reverted these changes, suggesting a critical role for these factors in activity-dependent motor cortical reorganization after ischemic lesion. These findings suggest that beneficial experience later in life can moderate adverse consequences of early programming to improve cerebrovascular health.
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    Maternal stress induces eipgenetic signatures of psychiatric and neurological diseases in the offspring
    (Public Library of Science, 2013) Zucchi, Fabiola C. R.; Yao, Youli; Ward, Isaac D.; Ilnytskyy, Yaroslav; Olson, David M.; Benzies, Karen; Kovalchuk, Igor; Kovalchuk, Olga; Metz, Gerlinde A. S.
    The gestational state is a period of particular vulnerability to diseases that affect maternal and fetal health. Stress during gestation may represent a powerful influence on maternal mental health and offspring brain plasticity and development. Here we show that the fetal transcriptome, through microRNA (miRNA) regulation, responds to prenatal stress in association with epigenetic signatures of psychiatric and neurological diseases. Pregnant Long-Evans rats were assigned to stress from gestational days 12 to 18 while others served as handled controls. Gestational stress in the dam disrupted parturient maternal behaviour and was accompanied by characteristic brain miRNA profiles in the mother and her offspring, and altered transcriptomic brain profiles in the offspring. In the offspring brains, prenatal stress upregulated miR-103, which is involved in brain pathologies, and downregulated its potential gene target Ptplb. Prenatal stress downregulated miR-145, a marker of multiple sclerosis in humans. Prenatal stress also upregulated miR-323 and miR-98, which may alter inflammatory responses in the brain. Furthermore, prenatal stress upregulated miR-219, which targets the gene Dazap1. Both miR-219 and Dazap1 are putative markers of schizophrenia and bipolar affective disorder in humans. Offspring transcriptomic changes included genes related to development, axonal guidance and neuropathology. These findings indicate that prenatal stress modifies epigenetic signatures linked to disease during critical periods of fetal brain development. These observations provide a new mechanistic association between environmental and genetic risk factors in psychiatric and neurological disease.
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    The progeny of Arabidopsis thaliana plants exposed to salt exhibit changes in DNA methylation, histone modifications and gene expression
    (Public Library of Science, 2012) Bilichak, Andriy; Ilnytskyy, Yaroslav; Hollunder, Jens; Kovalchuk, Igor
    Plants are able to acclimate to new growth conditions on a relatively short time-scale. Recently, we showed that the progeny of plants exposed to various abiotic stresses exhibited changes in genome stability, methylation patterns and stress tolerance. Here, we performed a more detailed analysis of methylation patterns in the progeny of Arabidopsis thaliana (Arabidopsis) plants exposed to 25 and 75 mM sodium chloride. We found that the majority of gene promoters exhibiting changes in methylation were hypermethylated, and this group was overrepresented by regulators of the chromatin structure. The analysis of DNA methylation at gene bodies showed that hypermethylation in the progeny of stressed plants was primarily due to changes in the 59 and 39 ends as well as in exons rather than introns. All but one hypermethylated gene tested had lower gene expression. The analysis of histone modifications in the promoters and coding sequences showed that hypermethylation and lower gene expression correlated with the enrichment of H3K9me2 and depletion of H3K9ac histones. Thus, our work demonstrated a high degree of correlation between changes in DNA methylation, histone modifications and gene expression in the progeny of salt-stressed plants.
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    Transgenerational adaptation of Arabidopsis to stress requires DNA methylation and the function of dicer-like proteins
    (Public Library of Science, 2010) Boyko, Alexander; Blevins, Todd; Yao, Youli; Golubov, Andrey; Bilichak, Andriy; Ilnytskyy, Yaroslav; Hollunder, Jens; Meins, Frederick; Kovalchuk, Igor
    Epigenetic states and certain environmental responses in mammals and seed plants can persist in the next sexual generation. These transgenerational effects have potential adaptative significance as well as medical and agronomic ramifications. Recent evidence suggests that some abiotic and biotic stress responses of plants are transgenerational. For example, viral infection of tobacco plants and exposure of Arabidopsis thaliana plants to UVC and flagellin can induce transgenerational increases in homologous recombination frequency (HRF). Here we show that exposure of Arabidopsis plants to stresses, including salt, UVC, cold, heat and flood, resulted in a higher HRF, increased global genome methylation, and higher tolerance to stress in the untreated progeny. This transgenerational effect did not, however, persist in successive generations. Treatment of the progeny of stressed plants with 5-azacytidine was shown to decrease global genomic methylation and enhance stress tolerance. Dicer-like (DCL) 2 and DCL3 encode Dicer activities important for small RNAdependent gene silencing. Stress-induced HRF and DNA methylation were impaired in dcl2 and dcl3 deficiency mutants, while in dcl2 mutants, only stress-induced stress tolerance was impaired. Our results are consistent with the hypothesis that stress-induced transgenerational responses in Arabidopsis depend on altered DNA methylation and smRNA silencing pathways.