DNA double-strand breaks (DSBs) are involved in many cellular mechanisms, including replication, transcription, and genome rearrangements. The recent observation that hot spots of DSBs in human chromosomes delimit DNA domains that possess coordinately expressed genes suggests a strong relationship between the organization of transcription patterns and hot spots of DSBs. In this study, we performed mapping of hot spots of DSBs in a human 43-kb ribosomal DNA (rDNA) repeated unit. We observed that rDNA units corresponded to the most fragile sites in human chromosomes and that these units possessed at least nine specific regions containing clusters of extremely frequently occurring DSBs, which were located exclusively in non-coding intergenic spacer (IGS) regions. The hot spots of DSBs corresponded to only a specific subset of DNase-hypersensitive sites, and coincided with CTCF, PARP1, and HNRNPA2B1 binding sites, and H3K4me3 marks. Our rDNA-4C data indicate that the regions of IGS containing the hot spots of DSBs often form contacts with specific regions in different chromosomes, including the pericentromeric regions, as well as regions that are characterized by H3K27ac and H3K4me3 marks, CTCF binding sites, ChIA-PET and RIP signals, and high levels of DSBs. The data suggest a strong link between chromosome breakage and several different mechanisms of epigenetic regulation of gene expression.

BackgroundThe molecular mechanisms that determine the organism's response to a variety of doses and modalities of stress factors are not well understood.ResultsWe studied effects of ionizing radiation (144, 360 and 864 Gy), entomopathogenic fungus (10 and 100 CFU), starvation (16 h), and cold shock (+4, 0 and -4°C) on an organism's viability indicators (survival and locomotor activity) and transcriptome changes in the Drosophila melanogaster model. All stress factors but cold shock resulted in a decrease of lifespan proportional to the dose of treatment. However, stress-factors affected locomotor activity without correlation with lifespan. Our data revealed both significant similarities and differences in differential gene expression and the activity of biological processes under the influence of stress factors.ConclusionsStudied doses of stress treatments deleteriously affect the organism's viability and lead to different changes of both general and specific cellular stress response mechanisms.

General and specific effects of molecular genetic responses to adverse environmental factors are not well understood. This study examines genome-wide gene expression profiles of Drosophila melanogaster in response to ionizing radiation, formaldehyde, toluene, and 2,3,7,8-tetrachlorodibenzo-p-dioxin. We performed RNA-seq analysis on 25,415 transcripts to measure the change in gene expression in males and females separately. An analysis of the genes unique to each treatment yielded a list of genes as a gene expression signature. In the case of radiation exposure, both sexes exhibited a reproducible increase in their expression of the transcription factors sugarbabe and tramtrack. The influence of dioxin up-regulated metabolic genes, such as anachronism, CG16727, and several genes with unknown function. Toluene activated a gene involved in the response to the toxins, Cyp12d1-p; the transcription factor Fer3’s gene; the metabolic genes CG2065, CG30427, and CG34447; and the genes Spn28Da and Spn3, which are responsible for reproduction and immunity. All significantly differentially expressed genes, including those shared among the stressors, can be divided into gene groups using Gene Ontology Biological Process identifiers. These gene groups are related to defense response, biological regulation, the cell cycle, metabolic process, and circadian rhythms. KEGG molecular pathway analysis revealed alteration of the Notch signaling pathway, TGF-beta signaling pathway, proteasome, basal transcription factors, nucleotide excision repair, Jak-STAT signaling pathway, circadian rhythm, Hippo signaling pathway, mTOR signaling pathway, ribosome, mismatch repair, RNA polymerase, mRNA surveillance pathway, Hedgehog signaling pathway, and DNA replication genes. Females and, to a lesser extent, males actively metabolize xenobiotics by the action of cytochrome P450 when under the influence of dioxin and toluene. Finally, in this work we obtained gene expression signatures pollutants (dioxin, toluene), low dose of gamma-irradiation and common molecular pathways for different kind of stressors.

BackgroundTranscriptional changes that contribute to the organism’s longevity and prevent the age-dependent decline of biological functions are not well understood. Here, we overexpressed pro-longevity gene encoding glutamate-cysteine ligase catalytic subunit (Gclc) and analyzed age-dependent changes in transcriptome that associated with the longevity, stress resistance, locomotor activity, circadian rhythmicity, and fertility.ResultsHere we reproduced the life extension effect of neuronal overexpression of the Gclc gene and investigated its influence on the age-depended dynamics of transcriptome and biological functions such as fecundity, spontaneous locomotor activity and circadian rhythmicity, as well as on the resistance to oxidative, proteotoxic and osmotic stresses. It was shown that Gclc overexpression reduces locomotor activity in the young and middle ages compared to control flies. Gclc overexpression slowed down the age-dependent decline of locomotor activity and circadian rhythmicity, and resistance to stress treatments. Gclc level demonstrated associations with the expression of genes involved in a variety of cellular processes including Jak-STAT, MAPK, FOXO, Notch, mTOR, TGF-beta signaling pathways, translation, protein processing in endoplasmic reticulum, proteasomal degradation, glycolysis, oxidative phosphorylation, apoptosis, regulation of circadian rhythms, differentiation of neurons, synaptic plasticity and transmission.ConclusionsOur study revealed that Gclc overexpression induces transcriptional changes associated with the lifespan extension and uncovered pathways that may be associated with the age-dependent decline of biological functions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3356-0) contains supplementary material, which is available to authorized users.

Multiple changes in the genome, transcriptome, and proteome are frequent in cancer cells. A search for molecular markers based on DNA, mRNA, or proteins is a main method to develop early specific diagnostics for cancer. While universal markers are still unavailable, similar trends are known for the expres sion patterns of particular genes in certain epithelial tumors. A bioinformatic screening of transcriptomic databases identified the NETO2 gene as a new potential promising marker of renal cancer. A substantial increase in NETO2 mRNA level was detected in 90% clear cell renal cell carcinomas, 70% of non small cell lung cancers, and 50% of papillary renal cancers by real time PCR. The NETO2 mRNA level was increased to a lesser extent in cervical carcinoma and colon cancer and tended to decrease in cancer of the stomach. The NETO2 gene, which codes for a membrane glycoprotein with an unclear function, was assumed to pro vide a new promising marker for early diagnosis in renal cancer and non small cell lung cancer.

One important question in aging research is how differences in genomics and transcriptomics determine the maximum lifespan in various species. Despite recent progress, much is still unclear on the topic, partly due to the lack of samples in nonmodel organisms and due to challenges in direct comparisons of transcriptomes from different species. The novel ranking‐based method that we employ here is used to analyze gene expression in the gray whale and compare its de novo assembled transcriptome with that of other long‐ and short‐lived mammals. Gray whales are among the top 1% longest‐lived mammals. Despite the extreme environment, or maybe due to a remarkable adaptation to its habitat (intermittent hypoxia, Arctic water, and high pressure), gray whales reach at least the age of 77 years. In this work, we show that long‐lived mammals share common gene expression patterns between themselves, including high expression of DNA maintenance and repair, ubiquitination, apoptosis, and immune responses. Additionally, the level of expression for gray whale orthologs of pro‐ and anti‐longevity genes found in model organisms is in support of their alleged role and direction in lifespan determination. Remarkably, among highly expressed pro‐longevity genes many are stress‐related, reflecting an adaptation to extreme environmental conditions. The conducted analysis suggests that the gray whale potentially possesses high resistance to cancer and stress, at least in part ensuring its longevity. This new transcriptome assembly also provides important resources to support the efforts of maintaining the endangered population of gray whales.

The genome expression pattern is strongly modified during the heat shock response (HSR) to form an adaptive state. This may be partly achieved by modulating microRNA levels that control the expression of a great number of genes that are embedded within the gene circuitry. Here, we investigated the cross-talk between two highly conserved and universal house-keeping systems, the HSR and microRNA machinery, in Drosophila melanogaster. We demonstrated that pronounced interstrain differences in the microRNA levels are alleviated after heat shock (HS) to form a uniform microRNA pattern. However, individual strains exhibit different patterns of microRNA expression during the course of recovery. Importantly, HS-regulated microRNAs may target functionally similar HS-responsive genes involved in the HSR. Despite the observed general downregulation of primary microRNA precursor expression as well as core microRNA pathway genes after HS, the levels of many mature microRNAs are upregulated. This indicates that the regulation of miRNA expression after HS occurs at transcriptional and post-transcriptional levels. It was also shown that deletion of all hsp70 genes had no significant effect on microRNA biogenesis but might influence the dynamics of microRNA expression during the HSR.

BackgroundGray whale, Eschrichtius robustus (E. robustus), is a single member of the family Eschrichtiidae, which is considered to be the most primitive in the class Cetacea. Gray whale is often described as a “living fossil”. It is adapted to extreme marine conditions and has a high life expectancy (77 years). The assembly of a gray whale genome and transcriptome will allow to carry out further studies of whale evolution, longevity, and resistance to extreme environment.ResultsIn this work, we report the first de novo assembly and primary analysis of the E. robustus genome and transcriptome based on kidney and liver samples. The presented draft genome assembly is complete by 55% in terms of a total genome length, but only by 24% in terms of the BUSCO complete gene groups, although 10,895 genes were identified. Transcriptome annotation and comparison with other whale species revealed robust expression of DNA repair and hypoxia-response genes, which is expected for whales.ConclusionsThis preliminary study of the gray whale genome and transcriptome provides new data to better understand the whale evolution and the mechanisms of their adaptation to the hypoxic conditions.Electronic supplementary materialThe online version of this article (doi: 10.1186/s12862-017-1103-z) contains supplementary material, which is available to authorized users.