DNA Methyltransferase Gene Research Articles

DNA Methyltransferase Genes Are Associated with Oral Mucositis and Creatinine Levels in Oncopediatric Patients.

The aim of this study was to investigate the association of single-nucleotide polymorphisms (SNPs) and the DNA methylation profiles of the DNA methyltransferase (DNMT) gene family with oral mucositis in children and adolescents with hematologic malignancies treated with methotrexate (MTX®). The population was comprised of healthy and oncopediatric patients aged between 4 and 19 years. An evaluation of oral conditions was performed using the Oral Assessment Guide. Demographic, clinical, hematological, and biochemical data were obtained from medical records. Genomic DNA extracted from oral mucosal cells was used for the analysis of polymorphisms in DNMT1 (rs2228611), DNMT3A (rs7590760), and DNMT3B (rs6087990) using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique (n = 102) and for DNA methylation using the methylation-specific PCR (MSP) technique (n = 85). The allele and genotypic frequencies of SNPs did not reveal any differences between patients with or without oral mucositis. An increase in the methylation frequency for DNMT1 in patients recovered from mucositis was detected. The DNMT3A methylated profile associated with the CC genotype (SNP rs7590760) appeared to be connected to higher values of creatinine. In addition, the DNMT3B unmethylated profile associated with the CC genotype (SNP rs6087990) appeared to be connected with higher values of creatinine. We conclude that the DNMT1 methylation profile is associated with the post-mucositis period and that the genetic and epigenetic profiles of DNMT3A and DNMT3B are associated with creatinine levels.

DNA methyltransferase expression (DNMT1, DNMT3a and DNMT3b) as a potential biomarker for anti-VEGF diabetic macular edema response.

DNA methylation is involved in Diabetic Retinopathy progression showing a metabolic memory mechanism. However, the association of DNA methyltransferase with diabetic macular edema is still unknown. We aimed to describe the differences in DNA methyltransferase gene expression in patients with different diabetic macular edema responses. A total of 27 diabetic patients, aged 59-90 years, were prospectively enrolled in this cross-sectional study. The participants were classified into control group (CG, n = 11), diabetic macular edema responders (rDME, n = 9) and non-responder diabetic macular edema (nrDME, n = 7) after anti-vascular endothelial growth factor (anti-VEGF) treatment. Only cases with a complete ophthalmological examination, digital 133° color fundus, and SD-OCT assessments were used. After RNA extraction and first-strand cDNA synthesis, quantitative real-time PCR was performed with specific primers on the CFX Connect™ Real-Time PCR Detection System to assess differential transcriptional expression patterns. The DNMT1 gene showed a positive correlation (r = 0.617; p = 0.043) with Best Corrected Visual Acuity (BCVA) in CG, a positive correlation (r = 0.917; p = 0.010) with HbA1c in nrDME and a negative correlation (r = -0.659; p = 0.049) with GCL-IPL thickness in rDME. DNMT3A gene showed a positive correlation (r = -0.890; p = 0.001) with Sub-foveal Choroidal thickness in rDME whereas DNMT3b gene showed a negative correlation (r = -0.815; p = 0.007) with HbA1c and RNFL (r = -0.664; p = 0.026) in CG. Patients with similar metabolic profile risk factors showed associated DNA methyltransferase transcriptional expression patterns differences fitting with the anti-VEGF diabetic macular edema response. Further studies are needed to clarify if these results (1) reflect disease evolution, (2) translate the therapeutic impact, (3) or can help to predict the therapeutic resistance profile.

Fruit Extract, Rich in Polyphenols and Flavonoids, Modifies the Expression of DNMT and HDAC Genes Involved in Epigenetic Processes.

Recently, the field of epigenetics has been intensively studied in relation to nutrition. In our study, the gene expression patterns of histone deacetylases (HDACs), which regulate the stability of histone proteins, and DNA methyltransferases (DNMTs), which regulate DNA methylation, were determined in mice. The animals were fed a human-equivalent dose of the aqueous extract of fruit seeds and peels, which is rich in flavonoids and polyphenols, for 28 days and then exposed to the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). The concentrations of trans-resveratrol and trans-piceid were determined in the consumed extract by HPLC and were 1.74 mg/L (SD 0.13 mg/L) and 2.37 mg/L (SD 0.32 mg/L), respectively, which corresponds to the consumption of 0.2-1 L of red wine, the main dietary source of resveratrol, in humans daily. Subsequently, 24 h after DMBA exposure, the expression patterns of the HDAC and DNMT genes in the liver and kidneys were determined by qRT-PCR. The DMBA-induced expression of the tested genes HDAC1, HDAC2, DNMT1, DNMT3A and DNMT3B was reduced in most cases by the extract. It has already been shown that inhibition of the DNMT and HDAC genes may delay cancer development and tumour progression. We hypothesise that the extract studied may exert chemopreventive effects.

Global DNA methylation, DNA methyltransferase and stress-related gene expression in ovine oocytes and embryos after exposure to metabolic stressors.

DNA methylation, considered the most prominent epigenetic mark was important for the gene regulation in embryonic development. The present study aimed at evaluating the effects of metabolic stressors [Non-esterified fatty acid (NEFA), β-hydroxy-butyric acid (BHB), ammonia and urea] exposure during the in vitro ovine oocyte maturation, global DNA methylation, DNA methyltransferase and stress-related gene expression. Colorimetric analysis of global DNA methylation and the expression of the DNA methyltransferase genes (DNMT1, DNMT3A, and DNMT3B) were assessed in the matured oocytes, 2-cell embryos and blastocysts produced in vitro from oocytes exposed with the metabolic stressors during 24 h of the in vitro maturation (IVM). Further, the mRNA expression of the stress-related genes (SOD1, SOD2) in the matured oocytes, 2-cell embryos and blastocysts produced was assessed. Significant difference in global DNA methylation levels between all the treatments tested was observed when compared with control in oocytes, two-cell embryos and blastocysts. Elevated concentration of metabolic stressors resulted in increased expressions of several stress-related genes, i.e., SOD1, SOD2 and in mRNA expression of DNA methyltransferase genes. The present study is the first to report that the DNA methylation was sensitive to the effects of the metabolic stressors in ovine oocytes/embryos. The aberrant expressions of genes during oocyte development targeted in the present study can provide evidence for the early embryo developmental arrest and blastocysts quality. These results highlighted the sensitivity of the early embryogenesis and more precisely of the reprogramming period to metabolites challenges, in a realistic situation of elevated concentration of metabolic stressors.

DNA methylation variation is crucial to restore adventitious rooting ability during in vitro shoot culture-induced rejuvenation in apple rootstock.

In vitro shoot culture has been widely used for restoring adventitious rooting ability in rooting recalcitrant woody perennial species for the past few decades, but its molecular mechanism is largely uncovered. DNA methylation is an essential epigenetic mark that participates in many biological processes. Recent reports suggested a role of DNA methylation in vitro culture in plants. In this study, we characterized the single-base resolution DNA methylome and transcriptome of adult and in vitro shoot culture-induced rejuvenation cuttings of apple rootstock M9T337. We found a global decrease in DNA methylation during rejuvenation, which may be correlated with increased expression of DNA demethylase genes and decreased expression of DNA methyltransferase genes. We additionally documented DNA hypomethylation in 'T337'_R in gene protomer associated with higher transcript levels of several adventitious rooting-related genes. The application of a DNA methylation inhibitor (5-azacytidine) enhanced the adventitious rooting ability and the expression level of adventitious rooting-related genes, such as, MdANT, MdMPK3, MdABCB21, MdCDC48, MdKIN8B, pri-MdMIR156a5 and pri-MdMIR156a12. Together, the DNA hypomethylation is critical for the rejuvenation-dependent adventitious rooting ability in apple rootstock. In addition, increased DNA methylation was also found in thousands of genes in 'T337'_R. We additionally documented that DNA hypermethylation is required for inhibition of adventitious rooting-repressed genes, such as MdGAD5a, encoding glutamate decarboxylase, which can catalyze glutamate decarboxylated to form γ-aminobutyric acid (GABA). Our results revealed that in vitro shoot culture-dependent DNA methylation variation plays important roles in adventitious rooting in apple rootstock.

Gene-wide significant association analyses of DNMT1 genetic variants with Parkinson's disease.

Background: DNA methylation plays an important role in Parkinson's disease (PD) pathogenesis. DNA methyltransferase 1 (DNMT1) is critical for maintaining DNA methylation in mammals. The link between DNMT1 polymorphisms and PD remains elusive. Methods: The DNMT1 gene contained a total of 28 single nucleotide polymorphisms (SNPs). Four representing tag-SNPs (rs16999593, rs2162560, rs11880553, and rs9305012) were identified and genotyped in a Han Chinese population comprising 712 PD patients and 696 controls. Association analyses were performed at gene-wide significance (p < 1.8 × 10-3). Results: Rs9305012, but not the other 3 tag-SNPs, was gene-wide significantly associated with PD risk (p = 0.8 × 10-3). The rs9305012/C was a protective allele against PD (p = 1.5 × 10-3, OR 0.786, 95% CI 0.677-0.912). No significant association was observed in individual genders or PD subtypes. Haplotypes of the 4 tag-SNPs showed a significant overall distribution difference between PD patients and controls (p < 1 × 10-4). The 3-allele ACC module in the order of rs2162560, rs11880553, and rs9305012 was the highest-risk haplotype associated with PD (p < 1 × 10-4, OR 2.439, 95% CI 1.563-3.704). Rs9305012 displayed certain probability to affect transcription factor binding and target gene expression based on functional annotation analyses. Conclusion: The DNMT1 variant rs9305012 together with its haplotypes may gene-wide significantly modulate PD susceptibility. Our results support a role of DNMT1 in PD pathogenesis and provide novel insights into the genetic connection in between.

Comprehensive analysis of the role of ICOS ( CD278 ) in pan-cancer prognosis and immunotherapy

BackgroundThe immunological checkpoint known as Inducible T Cell Costimulatory Factor (ICOS, Cluster of Differentiation, CD278) is activated and expressed on T cells. Both somatic cells and antigen-presenting cells expressed its ligand, ICOSL (including tumor cells in the tumor microenvironment).It is important for immunosuppression. Uncertainty surrounds the function of ICOS in tumor immunity.MethodsSeveral bioinformatics techniques were employed by us to thoroughly examine the expression and prognostic value of ICOS in 33 cancers based on data collected from TCGA and GTEx. In addition, ICOS was explored with pathological stage, tumor-infiltrating cells, immune checkpoint genes, mismatch repair (MMR) genes, DNA methyltransferases (DNMTs), microsatellite instability (MSI),and tumor mutation burden (TMB).In addition,To ascertain the level of ICOS expression in various cells, qRT-PCR was employed.ResultsThe findings revealed that ICOS expression was up regulation in most cancer types. The high expression of ICOS in tumor samples was related to the poor prognosis of UVM and LGG; The positive prognosis was boosted by the strong expression of ICOS in OV, SARC, SKCM, THYM, UCEC, and HNSC. The result is that the expression of malignancy was revealed by the immune cells’ invasion.profile of ICOS in different types of cancer. Different ways that ICOS expression is connected to immune cell infiltration account for variations in patient survival. Additionally, the TMB, MSI, MMR, and DNMT genes as well as ICOS expression are linked in many cancer types.The results of PCR showed that it is highly expressed in gastric, breast, liver and renal cell carcinoma cell lines compared with normal cells.ConclusionThis study suggests that ICOS may be a potential tumor immunotherapy target and prognostic marker.

Hepatic oleate regulates one-carbon metabolism during high carbohydrate feeding

Obesity is a major risk factor for type 2 diabetes, coronary heart disease, and strok. These diseases are associated with profound alterations in gene expression in metabolic tissues. Epigenetic-mediated regulation of gene expression is one mechanism through which environmental factors, such as diet, modify gene expression and disease predisposition. However, epigenetic control of gene expression in obesity and insulin resistance is not fully characterized. We discovered that liver-specific stearoyl-CoA desaturase-1 (Scd1) knockout mice (LKO) fed a high-carbohydrate low-fat diet exhibit dramatic changes in hepatic gene expression and metabolites of the folate cycle and one-carbon metabolism respectively for the synthesis of S-adenosylmethionine (SAM). LKO mice show an increased ratio of S-adenosylmethionine to S-adenosylhomocysteine, a marker for increased cellular methylation capacity. Furthermore, expression of DNA and histone methyltransferase genes is up-regulated while the mRNA and protein levels of the non-DNA methyltransferases including phosphatidylethanolamine methyltransferase (PEMT), Betaine homocysteine methyltransferase (Bhmt), and the SAM-utilizing enzymes such as glycine-N-methyltransferase (Gnmt) and guanidinoacetate methyltransferase (Gamt) are generally down-regulated. Feeding LKO mice a high carbohydrate diet supplemented with triolein, but not tristearin, and increased endogenous hepatic synthesis of oleate but not palmitoleate in Scd1 global knockout mice normalized one carbon gene expression and metabolite levels. Additionally, changes in one carbon gene expression are independent of the PGC-1α-mediated ER stress response previously reported in the LKO mice. Together, these results highlight the important role of oleate in maintaining one-carbon cycle homeostasis and point to observed changes in one-carbon metabolism as a novel mediator of the Scd1 deficiency-induced liver phenotype.

Homeobox protein A1-like and DNA methylation regulate embryo-specific Zinc finger protein 615 gene expression and embryonic development in the silkworm Bombyx mori.

DNA methylation and transcription factors play roles in gene expression and animal development. In insects, DNA methylation modifies gene bodies, but how DNA methylation and transcription factors regulate gene expression is unclear. In this study, we investigated the mechanism that regulates the expression of Bombyx mori Zinc finger protein 615 (ZnF 615), which is a downstream gene of DNA methyltransferase 1 (Dnmt1), and its effects on the regulation of embryonic development. By progressively truncating the ZnF 615 promoter, it was found that the -223 and -190nt region, which contains homeobox (Hox) protein cis-regulatory elements (CREs), had the greatest impact on the transcription of ZnF 615. RNA interference (RNAi)-mediated knockdown and overexpression of Hox family genes showed that Hox A1-like can enhance the messenger RNA level of ZnF 615. Further studies showed that Hox A1-like regulates ZnF 615 expression by directly binding to the -223 and -190nt region of its promoter. Simultaneous RNAi-mediated knockdown or overexpression of Hox A1-like and Dnmt1 significantly inhibited or enhanced the regulatory effect of either gene alone on ZnF 615 expression, suggesting that both DNA methylation of gene bodies and binding of transcription factors to promoters are essential for gene expression. RNAi-mediated knockdown of Hox A1-like and Dnmt1 showed that the embryonic development was retarded and the hatching rate was decreased. Taken together, these data suggest that Hox A1-like and DNA methylation enhance the expression of ZnF 615, thereby affecting the development of B. mori embryos.

Identification and gene expression analysis of cytosine-5 DNA methyltransferase and demethylase genes in Amaranthus cruentus L. under heavy metal stress.

Amaranth has become increasingly popular due to its highly nutritious grains and ability to tolerate environmental stress. The mechanism underlying defense and adaptation to environmental stress is a complicated process involving DNA methylation and demethylation. These epigenetic features have been well documented to play an important role in plant stress response, including heavy metal-induced stress. This study was aimed at the identification and analysis of cytosine-5 DNA methyltransferase (C5-MTase) and demethylase (DMTase) genes in Amaranthus cruentus. Eight C5-MTase and two DMTase genes were identified and described in response to individual heavy metals (Cd, Pb, Zn, Mn) and their combination (Cd/Pb, Cd/Zn, Pb/Zn) in root and leaf tissues. Studied heavy metals, individually and in combinations, differentially regulated C5-MTase and DMTase gene expression. Interestingly, most of the genes were transcriptionally altered under Zn exposure. Our results suggest that identified amaranth MTase and DMTase genes are involved in heavy metal stress responses through regulating DNA methylation and demethylation level in amaranth plants.

Investigation of the effects of the royal jelly on genomic demethylation and tumor suppressor genes in human cancer cells.

Royal jelly is a gelatinous nutrient secretion produced by the mandibular glands of young worker honey bees and has a critical role in honey bee life. In the honey bee colonies, queen and worker honey bees have very different morphologies and behaviors due to their diet in the larval period, despite having the same genome. In comparison, queen bees formed from larvae that feed royal jelly exclusively, and worker bees formed from larvae that feed on much less royal jelly. DNA methylation has been shown to play a critical role in the development of queen and worker honeybees. Alterations in DNA methylation, one of the epigenetic mechanisms defined as hereditable nucleotide modifications that occur in gene expression without changes in the DNA sequence, are closely related to many diseases, especially cancer. Hypermethylation of CpG islands located in the promoter regions of genes causes gene silencing and tumor suppressor genes epigenetically have silenced in cancer. The inactivation of tumor suppressor genes disrupts nearly all cellular pathways in cancer. In contrast to genetic alterations, gene silencing by epigenetic modifications may potentially be reversed and used in cancer treatment. Royal jelly, which causes epigenetic changes in bee colonies, has the potential to cause a change in cancer cells. In our study, royal jelly's effects on DNA methyltransferase enzyme and gene methylation of RASSF1A tumor suppressor were investigated in human cancer cell lines (HeLa, HT29, and A549), and modifications in the gene expression profile of royal jelly were determined by next generation sequencing.

The maternal effects of dietary restriction on Dnmt expression and reproduction in two clones of Daphnia pulex.

The inheritance of epigenetic marks induced by environmental variation in a previous generation is broadly accepted as a mediator of phenotypic plasticity. Transgenerational effects linking maternal experiences to changes in morphology, gene expression, and life history of successive generations are known across many taxa. While the number of studies linking epigenetic variation to ecological maternal effects is increasing rapidly, few if any attempts have been made to investigate molecular mechanisms governing epigenetic functions in the context of ecologically relevant maternal effects. Daphnia make an ideal model for investigating molecular epigenetic mechanisms and ecological maternal effects because they will reproduce asexually in the lab. Daphnia are also known to have strong maternal effects, involving a variety of traits and environmental variables. Using two clones of Daphnia pulex, we investigated the plasticity of life history and DNA methyltransferase (Dnmt) gene expression with respect to food limitation within and across generations. We found strong evidence of genotypic variation of responses of life history and Dnmt expression to low food diets, both within and across generations. In general, effects of offspring diet were larger than either the direct maternal effect or offspring-maternal environment interactions, but the direction of the maternal effect was usually in the opposite direction of the within-generation effect. For both life history and Dnmt expression, we also found that when offspring had low food, effects of the maternal environment were stronger than when offspring had high food.

Global and Regional DNA methylation silencing of PPARγ Associated with Glioblastoma Multiforme Pathogenesis.

The relationship between peroxisome proliferator-activated receptor gamma (PPARγ) expression level and epigenetic modifications occurring in glioblastoma multiforme (GBM) pathogenesis is largely unknown. Herein, we examine the association of PPARγ expression with its promoter and genomic global DNA methylation status, as well as DNA methyltransferases (DNMTs) gene expression in GBM patients. We examined the patterns of promoter methylation and PPARγ expression in 26 GBM tissues and 13 adjacent non-tumor tissues by methylation-specific PCR (MSP), real-time PCR, and ELISA, respectively. Also, we examined the genomic global 5-methyl cytosine levels and DNMTs gene expression using ELISA and real-time PCR methods, respectively. We found that hypermethylation on a specific region of the PPARγ promoter is significantly associated with the downregulation of the PPARγ gene and protein level in GBM patients. Interestingly, the amount of 5-methyl cytosine level was significantly reduced in GBM patients and positively correlated with PPARγ protein expression. Furthermore, the expression level of DNMT1, DNMT3A, and 3B were upregulated in GBM patients and the average expression level of all three DNMTs was positively correlated with tumor area. Also, we found that tumors from cortical regions exhibited a higher global DNA hypomethylation and PPARγ hypermethylation was related to the increase in GBM risk. Our study demonstrated that global DNA methylation and PPARγ epigenetic silencing is associated with the GBM risk. Our data provide a novel molecular mechanistic insight into epigenetic silencing of PPARγ in GBM patients that may be relevant as a key tumor marker for GBM pathogenesis.

A history of childhood maltreatment is associated with altered DNA methylation levels of DNA methyltransferase 1 in maternal but not neonatal mononuclear immune cells.

Childhood maltreatment (CM) is associated with alterations in DNA methylation (DNAm) especially in stress response genes. Due to the higher risk of overall health complications of individuals with a parental history of CM, intergenerational transmission of CM-associated DNAm changes has been investigated but remains unclear. In this study, we investigated if different severities of CM have any influence on the DNAm of DNA methyltransferase 1 (DNMT1), an important enzyme of the DNAm machinery, in immune and buccal cells of mother-newborn dyads. DNAm was assessed by mass spectrometry using immune cell DNA from mothers (N = 117) and their newborns (N = 113), and buccal cell DNA of mother-newborn dyads (N = 68 each). Mothers with a history of CM had lower mean methylation of DNMT1 in immune cells compared to the mothers without a CM history. CM status only influenced maternal DNMT1 gene expression when at least moderate CM was reported. Buccal cell DNAm was not associated with CM status. Maternal history of CM was not linked to any alterations in DNMT1 mean DNAm in any of the cell types studied in newborns. We conclude that the CM-associated alterations in DNMT1 DNAm might point to allostatic load and can be physiologically relevant, especially in individuals with more severe CM experiences, resulting in an activated DNA methylation machinery that might influence stress response genes. Our lack of significant findings in buccal cells shows the tissue-specific effects of CM on DNAm. In our sample with low to moderate maternal CM history, there was no intergenerational transmission of DNMT1 DNAm in newborns.

Using zebrafish embryo bioassays to identify chemicals modulating the regulation of the epigenome: a case study with simvastatin.

Contaminants of emerging concern have been increasingly associated with the modulation of the epigenome, leading to potentially inherited and persistent impacts on apical endpoints. Here, we address the performance of the OECD Test No. 236 FET (fish embryo acute toxicity) in the identification of chemicals able to modulate the epigenome. Using zebrafish (Danio rerio) embryos, acute and chronic exposures were performed with the pharmaceutical, simvastatin (SIM), a widely prescribed hypocholesterolemic drug reported to induce inter and transgenerational effects. In the present study, the epigenetic effects of environmentally relevant concentrations of SIM (from 8ng/L to 2000ng/L) were addressed following (1) an acute embryo assay based on OECD Test No. 236 FET, (2) a chronic partial life-cycle exposure using adult zebrafish (90days), and (3) F1 embryos obtained from parental exposed animals. Simvastatin induced significant effects in gene expression of key epigenetic biomarkers (DNA methylation and histone acetylation/deacetylation) in the gonads of exposed adult zebrafish and in 80 hpf zebrafish embryos (acute and chronic parental intergenerational exposure), albeit with distinct effect profiles between biological samples. In the chronic exposure, SIM impacted particularly DNA methyltransferase genes in males and female gonads, whereas in F1 embryos SIM affected mostly genes associated with histone acetylation/deacetylation. In the embryo acute direct exposure, SIM modulated the expression of both genes involved in DNA methylation and histone deacetylase. These findings further support the use of epigenetic biomarkers in zebrafish embryos in a high throughput approach to identify and prioritize epigenome-modulating chemicals.

Distinct global DNA methylation and NF-κB expression profile of preimplantation biopsies from ideal and non-ideal kidneys.

Epigenetic mechanisms may affect the ideal and non-ideal kidneys selected for transplantationand their inflammatory gene expression profile differently and may contribute to poor clinical outcomes. Study the Global DNA methylation and the expression profiles of the DNA methyltransferases (DNMTs) and nuclear factor kappa B (NF-κB) in preimplantation kidney biopsies from ideal and non-ideal kidneys (expanded criteria donor (ECD) and with KDPI > 85%). In a sample consistingof45 consecutive pre-implantation biopsies,global DNA methylation levels were detected by LINE-1 repeated elements using bisulfite pyrosequencing. DNMT gene expression was assessed by real-time quantitative polymerase chain reaction, and NF-κB protein expression by immunofluorescence. ECD kidneys displayed increased methylation levels in LINE-1, and DNMT1 and DNMT3B expression was upregulated when comparing ECD to standard criteria donor kidneys. Similarly, kidneys with KDPI > 85% exhibited increased LINE-1 methylation and DNMT1 upregulation when compared to a KDPI ≤ 85%. NF-κB protein expression levels were greatly increased in both types of non-ideal kidneys compared to ideal kidneys. Moreover, hypermethylation of LINE-1 was associated with cold ischemia time > 20h and ECD kidney classification. This study shows that global DNA hypermethylation and high expression of NF-κB occurred in both types of non-ideal kidneys and were associated with prolonged cold ischemia time. Global DNA methylation can be a useful tool to assess non-ideal kidneys and hence, could be used to expand the pool of kidneys donors.

Highly Contiguous Genome Assemblies of the Guinea Paper Wasp (Polistes exclamans) and Mischocyttarus mexicanus.

Paper wasps are a model system for the study of social evolution due to a high degree of inter- and intraspecific variation in cooperation, aggression, and visual signals of social status. Increasing the taxonomic coverage of genomic resources for this diverse clade will aid comparative genomic approaches for testing predictions about the molecular basis of social evolution. Here, we provide draft genome assemblies for two well-studied species of paper wasps, Polistes exclamans and Mischocyttarus mexicanus. The P. exclamans genome assembly is 221.5 Mb in length with a scaffold N50 of 4.11 Mb. The M. mexicanus genome assembly is 227 Mb in length with a scaffold N50 of 1.1 Mb. Genomes have low repeat content (9.54–10.75%) and low GC content (32.06–32.4%), typical of other social hymenopteran genomes. The DNA methyltransferase gene, Dnmt3 , was lost early in the evolution of Polistinae. We identified a second independent loss of Dnmt3 within hornets (genus: Vespa).

LncRNA RP3-525N10.2-NFKB1-PROS1 triplet-mediated low PROS1 expression is an onco-immunological biomarker in low-grade gliomas: a pan-cancer analysis with experimental verification

BackgroundGlioma is the most common cancer in the central nervous system, and low grade gliomas are notorious for many types of tumors and heterogeneity. PROS1 not only plays an important role in the blood coagulation system, and recent studies have found that it was correlated with the development of tumors, especially related to tumor immune infiltration. However, the study of underlying role and mechanism of PROS1 in gliomas, especially in low-grade gliomas, is almost absent.MethodsWe integrated the information of patients with LGG in The Cancer Genome Atlas (TCGA) cohort and Chinese Glioma Genome Atlas (CGGA) cohort. Then, we systematically demonstrated the differences and prognostic prognosis value of PROS1 based on multi-omics analyses. In addition, Cell counting kit-8 (CCK-8) assay, colony formation assay, 5-Ethynyl-2’-deoxyuridine (EdU) incorporation assay, and Transwell assays were performed to evaluate cell proliferation and invasion. qRT-PCR and immunohistochemistry were used to evaluate the expression of PROS1 in LGG.ResultsVarious bioinformatics approaches revealed that PROS1 was a valuable prognostic marker and may influence tumour development via distinct mechanisms, including expression of DNA methyltransferase, RNA modification, and DNA mismatch repair system genes, copy number variation, single nucleotide variation frequency, genomic heterogeneity, cancer stemness, DNA methylation, and alternative PROS1 splicing. Our analyses indicated that the long non-coding RNA RP3-525N10.2 may “decoy” or “guide” the transcription factor NFKB1 and prevent its association with PROS1, thereby reducing PROS1 expression and improving poor LGG prognosis. PROS1 expression was also closely associated with tumour infiltration by immune cells, especially tumour-associated macrophages, as well as the expression of various immune checkpoint inhibitors, immunomodulators, and immune cell markers.Conclusionlong non-coding RNA RP3-525N10.2-NFKB1-PROS1 triplet-mediated PROS1 expression could serve as a biomarker for cancer diagnosis, prognosis, therapy selection, and follow-up in LGG patients.

DNA hypermethylation promotes the flowering of orchardgrass during vernalization.

Vernalization, influenced by environmental factors, is an essential process associated with the productivity of temperate crops, during which epigenetic regulation of gene expression plays an important role. Although DNA methylation is one of the major epigenetic mechanisms associated with the control of gene expression, global changes in DNA methylation in the regulation of gene expression during vernalization-induced flowering of temperate plants remain largely undetermined. To characterize vernalization-associated DNA methylation dynamics, we performed whole-genome bisulfite-treated sequencing and transcriptome sequencing in orchardgrass (Dactylis glomerata) during vernalization. The results revealed that increased levels of genome DNA methylation during the early vernalization of orchardgrass were associated with transcriptional changes in DNA methyltransferase and demethylase genes. Upregulated expression of vernalization-related genes during early vernalization was attributable to an increase in mCHH in the promoter regions of these genes. Application of an exogenous DNA methylation accelerator or overexpression of orchardgrass NUCLEAR POLY(A) POLYMERASE (DgPAPS4) promoted earlier flowering, indicating that DNA hypermethylation plays an important role in vernalization-induced flowering. Collectively, our findings revealed that vernalization-induced hypermethylation is responsible for floral primordium initiation and development. These observations provide a theoretical foundation for further studies on the molecular mechanisms underlying the control of vernalization in temperate grasses.

Evaluation of the initial manifestations of the toxic process in conditions of chronic action of low subtoxic doses of dioxins polluting the environment

AIM: To study the state of the genome by indicators of retrotransposon activity the gene encoding DNA methyltransferase 1 (DNMT1); DNA damage in animals from the natural population of the bank vole (Clethrionomys glareolus) living in the vicinity of a preserved landfill contaminated with low concentrations of dioxins (landfill of production and consumption waste "Salariyevo", Moscow).&#x0D; MATERIAL AND METHODS: The activity of ERV-L, B1, and L1 retrotransposons and the transcription level of the DNMT1 gene were evaluated by real-time PCR. The stability of DNA in liver and bone marrow cells was characterized by the comet assay method. Afterward, the obtained characteristics of the state (stability, reactivity, and damage) of the genome in response to environmental stress factors were compared in groups of animals from the study and conditionally control samples.&#x0D; RESULTS: The effects of a decrease in the activity of retrotransposons of classes B1 and L1, and an increase in DNMT1 gene expression level were revealed in voles from the natural population living under the long-term chronic exposure to low doses of dioxins decrease in the activity of retrotransposons of classes B1 and L1, and an increase in the expression level of the DNMT1 gene were revealed. An increased level of DNA damage (on average up to 56% of the DNA in the tail of the comet) was detected in hepatocytes, with the addition of winter environmental factors to the chronic effect of small subtoxic doses of dioxins.&#x0D; CONCLUSION: Suppression of retrotransposon activity and increased expression of its epigenetic regulator (DNMT1) are regarded as adaptive responses to long-term chronic exposure to low doses of dioxins polluting the environment. The alteration in the reactivity and destabilization of the genome indicates the launch of the initial mechanisms of the toxic process formation. The created and tested methodological base for its study opens up prospects for establishing a threshold level, and as a result, substantiating indicators for screening assessment of local (territorial) risk to public health by biomonitoring.