Kovalchuk, Igor
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- ItemRole of epigenetic factors in response to stress and establishment of somatic memory of stress exposure in plants(MDPI, 2023) Kovalchuk, IgorAll species are well adapted to their environment. Stress causes a magnitude of biochemical and molecular responses in plants, leading to physiological or pathological changes. The response to various stresses is genetically predetermined, but is also controlled on the epigenetic level. Most plants are adapted to their environments through generations of exposure to all elements. Many plant species have the capacity to acclimate or adapt to certain stresses using the mechanism of priming. In most cases, priming is a somatic response allowing plants to deal with the same or similar stress more efficiently, with fewer resources diverted from growth and development. Priming likely relies on multiple mechanisms, but the differential expression of non-coding RNAs, changes in DNA methylation, histone modifications, and nucleosome repositioning play a crucial role. Specifically, we emphasize the role of BRM/CHR17, BRU1, FGT1, HFSA2, and H2A.Z proteins as positive regulators, and CAF-1, MOM1, DDM1, and SGS3 as potential negative regulators of somatic stress memory. In this review, we will discuss the role of epigenetic factors in response to stress, priming, and the somatic memory of stress exposures.
- ItemGenomic and epigenomic changes in the progeny of cold-stressed Arabidopsis thaliana plants(MDPI, 2024) Rahman, Ashif; Yadav, Narendra Singh; Byeon, Boseon; Ilnytskyy, Yaroslav; Kovalchuk, IgorPlants 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.
- ItemRelationship between desiccation tolerance and biofilm formation in shiga toxin-producing Escherichia coli(MDPI, 2024) Javed, Muhammad Qasim; Kovalchuk, Igor; Yevtushenko, Dmytro P.; Yang Xianqin; Stanford, KimShiga toxin-producing Escherichia coli (STEC) is a major concern in the food industry and requires effective control measures to prevent foodborne illnesses. Previous studies have demonstrated increased difficulty in the control of biofilm-forming STEC. Desiccation, achieved through osmotic stress and water removal, has emerged as a potential antimicrobial hurdle. This study focused on 254 genetically diverse E. coli strains collected from cattle, carcass hides, hide-off carcasses, and processing equipment. Of these, 141 (55.51%) were STEC and 113 (44.48%) were generic E. coli. The biofilm-forming capabilities of these isolates were assessed, and their desiccation tolerance was investigated to understand the relationships between growth temperature, relative humidity (RH), and bacterial survival. Only 28% of the STEC isolates had the ability to form biofilms, compared to 60% of the generic E. coli. Stainless steel surfaces were exposed to different combinations of temperature (0 °C or 35 °C) and relative humidity (75% or 100%), and the bacterial attachment and survival rates were measured over 72 h and compared to controls. The results revealed that all the strains exposed to 75% relative humidity (RH) at any temperature had reduced growth (p < 0.001). In contrast, 35 °C and 100% RH supported bacterial proliferation, except for isolates forming the strongest biofilms. The ability of E. coli to form a biofilm did not impact growth reduction at 75% RH. Therefore, desiccation treatment at 75% RH at temperatures of 0 °C or 35 °C holds promise as a novel antimicrobial hurdle for the removal of biofilm-forming E. coli from challenging-to-clean surfaces and equipment within food processing facilities.
- ItemDepletion of eukaryotic initiation factor 5B (eIF5B) reprograms the cellular transcriptome and leads to activation of endoplasmic reticulum (ER) stress and c-Jun N-terminal Kinase (JNK).(Springer, 2021) Bressler, Kamiko R.; Ross, Joseph A.; Ilnytskyy, Slava; Vanden Dungen, Keiran; Taylor, Katrina; Patel, Kush; Zovoilis, Athanasios; Kovalchuk, Igor; Thakor, NehalDuring the integrated stress response (ISR), global translation initiation is attenuated; however, noncanonical mechanisms allow for the continued translation of specific transcripts. Eukaryotic initiation factor 5B (eIF5B) has been shown to play a critical role in canonical translation as well as in noncanonical mechanisms involving internal ribosome entry site (IRES) and upstream open reading frame (uORF) elements. The uORF-mediated translation regulation of activating transcription factor 4 (ATF4) mRNA plays a pivotal role in the cellular ISR. Our recent study confirmed that eIF5B depletion removes uORF2-mediated repression of ATF4 translation, which results in the upregulation of growth arrest and DNA damage-inducible protein 34 (GADD34) transcription. Accordingly, we hypothesized that eIF5B depletion may reprogram the transcriptome profile of the cell. Here, we employed genome-wide transcriptional analysis on eIF5B-depleted cells. Further, we validate the up- and downregulation of several transcripts from our RNA-seq data using RT-qPCR. We identified upregulated pathways including cellular response to endoplasmic reticulum (ER) stress, and mucin-type O-glycan biosynthesis, as well as downregulated pathways of transcriptional misregulation in cancer and T cell receptor signaling. We also confirm that depletion of eIF5B leads to activation of the c-Jun N-terminal kinase (JNK) arm of the mitogen-activated protein kinase (MAPK) pathway. This data suggests that depletion of eIF5B reprograms the cellular transcriptome and influences critical cellular processes such as ER stress and ISR.
- ItemEnvironmental 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.