Background:The conserved ATP-dependent chromatin remodeling enzyme Fun30 regulates heterochromatin silencing and DNA repair. Results: Gene expression is up-regulated, and nucleosome positioning is altered in fun30⌬ cells, and purified Fun30 slides nucleosome in vitro. Conclusion: Fun30 represses gene expression by sliding promoter-proximal nucleosomes. Significance: The function of Fun30 is expanded to regulation of transcription and chromatin remodeling by nucleosome sliding.

Recent research shows that chemotherapy agents can be more toxic to healthy brain cells than to the target cancer cells. They cause a range of side effects, including memory loss and cognitive dysfunction that can persist long after the completion of treatment. This condition is known as chemo brain. The molecular and cellular mechanisms of chemo brain remain obscure. Here, we analyzed the effects of two cytotoxic chemotherapy drugs—cyclophosphamide (CPP) and mitomycin C (MMC) - on transcriptomic and epigenetic changes in the murine prefrontal cortex (PFC) and hippocampal regions. We for the first time showed that CPP and MMC treatments led to profound sex- and brain region-specific alterations in gene expression profiles. Gene expression changes were most prominent in the PFC tissues of female mice 3 weeks after MMC treatment, and the gene expression response was much greater for MCC than CPP exposure. MMC exposure resulted in oxidative DNA damage, evidenced by accumulation of 8-oxo-2′-deoxyguanosine (8-oxodG) and a decrease in the level of 8-oxodG repair protein OGG1 in the PFC of female animals 3 weeks after treatment. MMC treatment decreased global DNA methylation and increased DNA hydroxymethylation in the PFC tissues of female mice. The majority of the changes induced by chemotherapy in the PFC tissues of female mice resembled those that occur during the brain's aging processes. Therefore, our study suggests a link between chemotherapy-induced chemo brain and brain aging, and provides an important roadmap for future analysis.

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Core Ideas Progeny of heat‐stressed Brassica rapa plants exhibit changes in abundance of tRFs and snoRFs Regulation of ER via isoacceptors may be an essential component of transgenerational response tRFs regulating brassinosteroid metabolism may contribute to stress tolerance in the progeny Epigenetic regulations in the form of changes in differential expression of noncoding RNAs (ncRNAs) are an essential mechanism of stress response in plants. Previously we showed that heat treatment in Brassica rapa L. results in the differential processing and accumulation of ncRNA fragments (ncRFs) stemming from transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), small nuclear RNAs (snRNAs), and small nucleolar RNAs (snoRNAs). In this work, we analyzed whether ncRFs are differentially expressed in the progeny of heat‐stressed plants. We found significant changes in the size of tRF reads and a significant decrease in the percentage of tRFs mapping to tRNA‐Ala, tRNA‐Arg, and tRNA‐Tyr and an increase in tRFs mapping to tRNA‐Asp. The enrichment analysis showed significant differences in processing of tRFs from tRNAAla(AGC), tRNAAla(UGC), tRNAArg(UGC), tRNAThr(UGU), tRNAPseudo(UCC), and tRNAVal(CAC) isoacceptors. Analysis of potential targets of tRFs showed that they regulate brassinosteroid metabolism, the proton pump ATPase activity, the antiporter activity, the mRNA decay activity as well as nucleosome positioning and the epigenetic regulation of transgenerational response. Gene ontology term analysis of potential targets demonstrated a significant enrichment in tRFs that potentially targeted a cellular component endoplasmic reticulum (ER) and in small nucleolar RNA fragments (snoRFs), the molecular function protein binding. To summarize, our work demonstrated that the progeny of heat‐stressed Brassica rapa plants exhibit changes in the expression of tRFs and snoRFs but not of small nuclear RNA fragments (snRFs) or ribosomal RNA fragments (rRFs) and these changes likely better prepare the progeny of stressed plants to future stress encounters.

Plants are sedentary organisms that constantly sense changes in their environment and react to various environmental cues. On a short-time scale, plants respond through alterations in their physiology, and on a long-time scale, plants alter their development and pass on the memory of stress to the progeny. The latter is controlled genetically and epigenetically and allows the progeny to be primed for future stress encounters, thus increasing the likelihood of survival. The current study intended to explore the effects of multigenerational heat stress in Arabidopsis thaliana. Twenty-five generations of Arabidopsis thaliana were propagated in the presence of heat stress. The multigenerational stressed lineage F25H exhibited a higher tolerance to heat stress and elevated frequency of homologous recombination, as compared to the parallel control progeny F25C. A comparison of genomic sequences revealed that the F25H lineage had a three-fold higher number of mutations [single nucleotide polymorphisms (SNPs) and insertions and deletions (INDELs)] as compared control lineages, suggesting that heat stress induced genetic variations in the heat-stressed progeny. The F25H stressed progeny showed a 7-fold higher number of non-synonymous mutations than the F25C line. Methylome analysis revealed that the F25H stressed progeny showed a lower global methylation level in the CHH context than the control progeny. The F25H and F25C lineages were different from the parental control lineage F2C by 66,491 and 80,464 differentially methylated positions (DMPs), respectively. F25H stressed progeny displayed higher frequency of methylation changes in the gene body and lower in the body of transposable elements (TEs). Gene Ontology analysis revealed that CG-DMRs were enriched in processes such as response to abiotic and biotic stimulus, cell organizations and biogenesis, and DNA or RNA metabolism. Hierarchical clustering of these epimutations separated the heat stressed and control parental progenies into distinct groups which revealed the non-random nature of epimutations. We observed an overall higher number of epigenetic variations than genetic variations in all comparison groups, indicating that epigenetic variations are more prevalent than genetic variations. The largest difference in epigenetic and genetic variations was observed between control plants comparison (F25C vs. F2C), which clearly indicated that the spontaneous nature of epigenetic variations and heat-inducible nature of genetic variations. Overall, our study showed that progenies derived from multigenerational heat stress displayed a notable adaption in context of phenotypic, genotypic and epigenotypic resilience.