scholarly journals No effect of acute exercise on the dynamic change in the expression of genes involved in epigenetic modification in professional athletes

Author(s):  
Witold Józef Światowy ◽  
Jacek Zieliński ◽  
Maria Aleksandra Osielska ◽  
Krzysztof Kusy ◽  
Dariusz Wieliński ◽  
...  

Abstract Background:The adaptation of the organism to exercise in the context of gene expression profile is an interesting phenomenon. Exercise can change the expression of individual genes due to changes in the degree of DNA methylation, changes in miRNA expression, or through methylation or acetylation of histones.Hypothesis:Acute exercise increases the expression of genes such as HDAC1, DNMT1, and JHDM1D that can affect epigenetic modifications in PBMCs.Methods:The aim of this study was to determine whether there was a change in gene expression in the blood cells during acute exercise and after a 1-hour recovery. The transcriptions of genes involved in epigenetic modifications (HDAC1, HDAC1 and JHDM1D) were examined in 9 professional athletes at rest, during consecutive stages of a treadmill exercise until exhaustion, and following recovery.Results:No significant differences in the level of transcript were observed in the course of the experiment in the tested PBMC cells. On the other hand, a significant (p = 0.007) correlation was observed in the level of the JHDM1D gene transcript and the number of monocytes in the samples obtained after reaching peak exercise intensity, but in the initial samples this correlation was not significant (p = 0.053).Conclusion:Acute physical exercise does not rapidly alter the transcript levels of the JHDM1D, DNMT1 and HDAC1 genes in PBMCs. The observed correlation between the level of JHDM1D mRNA and the level of monocytes and HDAC1 with lymphocytes requires further investigation.

2018 ◽  
Vol 40 (01) ◽  
pp. 62-70 ◽  
Author(s):  
Alexander Schenk ◽  
Walter Pulverer ◽  
Christine Koliamitra ◽  
Claus Bauer ◽  
Suzana Ilic ◽  
...  

AbstractPositive effects of exercise on cancer prevention and progression have been proposed to be mediated by stimulating natural killer (NK) cells. Because NK cell receptors are regulated by epigenetic modifications, we investigated whether acute aerobic exercise and training change promoter DNA methylation and gene expression of the activating KIR2DS4 and the inhibiting KIR3DL1 gene. Sixteen healthy women (50–60 years) performed a graded exercise test (GXT) and were randomized into either a passive control group or an intervention group performing a four-week endurance exercise intervention. Blood samples (pre-, post-GXT and post-training) were used for isolation of DNA/RNA of NK cells to assess DNA promoter methylation by targeted deep-amplicon sequencing and gene expression by qRT-PCR. Potential changes in NK cell subsets were determined by flow cytometry. Acute and chronic exercise did not provoke significant alterations of NK cell proportions. Promoter methylation decreased and gene expression increased for KIR2DS4 after acute exercise. A high gene expression correlated with a low methylation of CpGs that were altered by acute exercise. Chronic exercise resulted in a minor decrease of DNA methylation and did not alter gene expression. Acute exercise provokes epigenetic modifications, affecting the balance between the activating KIR2DS4 and the inhibiting KIR3DL1, with potential benefits on NK cell function.


Reproduction ◽  
2007 ◽  
Vol 133 (1) ◽  
pp. 85-94 ◽  
Author(s):  
Shun-ichiro Kageyama ◽  
Honglin Liu ◽  
Naoto Kaneko ◽  
Masatoshi Ooga ◽  
Masao Nagata ◽  
...  

During oocyte growth, chromatin structure is altered globally and gene expression is silenced. To investigate the involvement of epigenetic modifications in the regulation of these phenomena, changes in global DNA methylation and in various histone modifications, i.e. acetylation of H3K9, H3K18, H4K5, and H4K12, and methylation of H3K4 and H3K9, were examined during the growth of mouse oocytes. Immunocytochemical analysis revealed that the signal intensities of all these modifications increased during growth and that fully grown, germinal vesicle (GV)-stage oocytes showed the most modifications. Since acetylation of most of the lysine residues on histones and methylation of H3K4 are associated with active gene expression, the increased levels of these modifications do not seem to be associated with gene silencing in GV-stage oocytes. Given that there are two types of GV-stage oocytes with different chromatin configurations and transcriptional activities, the epigenetic modification statuses of these two types were compared. The levels of all the epigenetic modifications examined were higher in the SN(surrounded nucleolus)-type oocytes, in which highly condensed chromatin is concentrated in the area around the nucleolus and gene expression is silenced than in the NSN(not surrounded nucleolus)-type oocytes, in which less-condensed chromatin does not surround the nucleolus and gene expression is active. In addition, the expression levels of various enzymes that catalyze histone modifications were shown by RT-PCR to increase with oocyte growth. Taken together, the results show that all of the epigenetic modifications increased in a concerted manner during oocyte growth, and suggest that these increases are not associated with gene expression.


2021 ◽  
Vol 12 (4) ◽  
pp. 4348-4356

Acute exercise induces rapid and dramatic induction of transcription in the liver. The beneficial effects of carnitine on serum factors and gene expression have been proven. This study examined the interaction between acute exercise and carnitine supplementation on the expression of genes involved in liver metabolism. Thirty-two male Wistar rats were randomly assigned into 4 groups (n = 8): Group 1 control, Group 2 received 200 mg/kg/day LCAR, Group 3 performed acute exercise, and Group 4 received LCAR and performed acute exercise. Gene expression in the liver was evaluated by Real-time PCR. Acute exercise significantly increased PDK4 expression compared to other groups. Also, carnitine administration, performing an acute exercise, and combination of LCAR-Acute significantly increased AMPK and PGC-1a expression compared with the control group. The expression of SREBP-1c and SCD1 was not significantly changed between studies. The combination of acute exercise and carnitine administration increased PGC-1a expression, indicating the importance of carnitine with exercise as a beneficial supplement.


Author(s):  
Jiaqi Li ◽  
Lifang Li ◽  
Xiaoxiao Sun ◽  
Tuo Deng ◽  
Gan Huang ◽  
...  

Accumulated evidence indicates that epigenetic modifications play central roles in gene expression regulation and participate in developing many autoimmune and autoinflammatory diseases. Mechanistically, epigenetic modifications act as a bridge between environmental and cellular factors and susceptibility genes. DNA methylation is a critical epigenetic modification that is regulated by ten-eleven translocation (TET) enzymes. Accumulating evidence has revealed that TET family proteins function as gene regulators and antitumor drug targets mainly because of their ability to oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Recently, the effect of Tet2, an essential TET protein, on the development of autoimmune diseases has been explored. In this review, we summarize the current understanding of Tet2 in immune response regulation, clarify the mechanisms of Tet2 in B and T cell differentiation and function, and discuss the opposing effects of Tet2 on inflammatory gene expression in the immune system to provide new potential therapeutic targets for related diseases.


PeerJ ◽  
2019 ◽  
Vol 6 ◽  
pp. e5840 ◽  
Author(s):  
Jeongwoo Kwon ◽  
Ying-Hua Li ◽  
Yu-Jin Jo ◽  
YoungJin Oh ◽  
Suk Namgoong ◽  
...  

Inhibition of both MEK1/2 and glycogen synthase kinase-3 (GSK3; 2i system) facilitates the maintenance of naïve stemness for embryonic stem cells in various mammalian species. However, the effect of the inhibition of the 2i system on porcine early embryogenesis is unknown. We investigated the effect of the 2i system on early embryo development, expression of pluripotency-related genes, and epigenetic modifications. Inhibition of MEK1/2 (by PD0325901) and/or GSK3 (by CHIR99021) did not alter the developmental potential of porcine parthenogenetic embryos, but improved blastocyst quality, as judged by the blastocyst cell number, diameter, and reduction in the number of apoptotic cells. The expression levels of octamer-binding transcription factor 4 and SOX2, the primary transcription factors that maintain embryonic pluripotency, were significantly increased by 2i treatments. Epigenetic modification-related gene expression was altered upon 2i treatment. The collective results indicate that the 2i system in porcine embryos improved embryo developmental potential and blastocyst quality by regulating epigenetic modifications and pluripotency-related gene expression.


2012 ◽  
Vol 24 (1) ◽  
pp. 216 ◽  
Author(s):  
M. K. Addison ◽  
L. W. Coley ◽  
G. T. Gentry ◽  
R. A. Godke ◽  
K. R. Bondioli

Bovine adipose-derived stem cells (ASC), a form of adult stem cells, are somatic cells that have similar characteristics of embryonic stem (ES) cells. ASC are multipotent and have been found to express genes associated with pluripotency, Oct4, Sox2 and Nanog. The unique properties of ASC make them a desirable source for reprogramming experiments. When somatic cells are reprogrammed, there are certain epigenetic changes or modifications that must occur. Epigenetic modifications will change the chromatin configuration without changing the DNA sequence. Somatic cells can be exposed to small molecules that induce some of these changes. Two epigenetic modifying factors are a DNA methyltranferase inhibitor, zebularine (Zeb) and a histone deacetylase inhibitor, valproic acid (VPA). By altering gene expression with these epigenetic modifiers, the cells may be stimulated to reprogram more efficiently than untreated cells. Three lines of bovine ASC were isolated from the stromal fraction of adipose tissue and expanded through 3 passages in DMEM (high glucose) supplemented with 10% fetal bovine serum. Cells were cultured by addition of 5 mM VPA or 100 μM Zeb to the culture medium and cultured for 5, 7, 10 or 14 days before mRNA was isolated and converted to cDNA. Control groups, consisting of untreated bovine ASC from the same cell lines, were cultured for the same time periods as the treatment groups. Quantitative RT-PCR was performed to determine transcript levels for Oct4, Sox2, Nanog and poly adenylate polymerase (PAP) as a reference gene. Transcript levels were quantified by relative quantification using the ΔΔCT method and expressed as ratios of the target genes (Oct4, Sox2 and Nanog) to the reference gene (PAP) and normalized against a calibrator consisting of untreated bovine ADS cells. Normalized ratios were log-transformed before analysis by ANOVA to correct for lack of normality. A one-way ANOVA was completed to test the statistical significance among the control and treatment groups. Pairwise comparison was conducted to test expression levels between individual treatments. When cells were treated for 5 days, Oct4 and Nanog expression levels were increased (P ≤ 0.05) between the control and both treatment groups. Expression of Sox2 was not different (P = 0.06) across treatment groups. Based on pair wise comparisons gene expression in VPA and Zeb treated groups were not different. Treatment for 7, 10, or 14 days did not result in any difference in transcript levels between the treatment groups and control for any of the genes analysed. VPA and Zeb treatment for 5 days may have produced a partial reprogramming. This partial reprogramming could aid in the bovine ASC reaching complete pluripotency when combined with other reprogramming techniques. This work was financed in part by a grant from the LSU System for the ACRES/LSU Collaborative Research Program.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Koji Hayakawa ◽  
Kenta Nishitani ◽  
Satoshi Tanaka

AbstractEpigenetic mechanisms can establish and maintain mitotically stable patterns of gene expression while retaining the DNA sequence. These mechanisms can be affected by environmental factors such as nutrients. The importance of intracellular dosages of nutrient metabolites such as acetyl coenzyme A and S-adenosylmethionine, which are utilized as donors for post-translational modifications, is well-known in epigenetic regulation; however, the significance of indirect metabolites in epigenetic regulation is not clear. In this study, we screened for metabolites that function as epigenetic modulators. Because the expression of genes related to hypothalamic function is reportedly affected by nutritional conditions, we used a neural cell culture system and evaluated hypothalamic-linked loci. We supplemented the culture medium with 129 metabolites separately during induction of human-iPS-derived neural cells and used high-throughput ChIP-qPCR to determine the epigenetic status at 37 hypothalamus-linked loci. We found three metabolites (kynurenine, 3-OH-kynurenine, and anthranilate) from tryptophan pathways that increased H3K4 trimethylation and H2AS40 O-GlcNAcylation, resulting in upregulated gene expression at most loci, except those encoding pan-neural markers. Dietary supplementation of these three metabolites and the resulting epigenetic modification were important for stability in gene expression. In conclusion, our findings provide a better understanding of how nutrients play a role in epigenetic mechanisms.


2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Brennan Hyden ◽  
Craig H. Carlson ◽  
Fred E. Gouker ◽  
Jeremy Schmutz ◽  
Kerrie Barry ◽  
...  

AbstractSex dimorphism and gene expression were studied in developing catkins in 159 F2 individuals from the bioenergy crop Salix purpurea, and potential mechanisms and pathways for regulating sex development were explored. Differential expression, eQTL, bisulfite sequencing, and network analysis were used to characterize sex dimorphism, detect candidate master regulator genes, and identify pathways through which the sex determination region (SDR) may mediate sex dimorphism. Eleven genes are presented as candidates for master regulators of sex, supported by gene expression and network analyses. These include genes putatively involved in hormone signaling, epigenetic modification, and regulation of transcription. eQTL analysis revealed a suite of transcription factors and genes involved in secondary metabolism and floral development that were predicted to be under direct control of the sex determination region. Furthermore, data from bisulfite sequencing and small RNA sequencing revealed strong differences in expression between males and females that would implicate both of these processes in sex dimorphism pathways. These data indicate that the mechanism of sex determination in Salix purpurea is likely different from that observed in the related genus Populus. This further demonstrates the dynamic nature of SDRs in plants, which involves a multitude of mechanisms of sex determination and a high rate of turnover.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Jonathan D. Licht ◽  
Richard L. Bennett

Abstract Background Epigenetic mechanisms regulate chromatin accessibility patterns that govern interaction of transcription machinery with genes and their cis-regulatory elements. Mutations that affect epigenetic mechanisms are common in cancer. Because epigenetic modifications are reversible many anticancer strategies targeting these mechanisms are currently under development and in clinical trials. Main body Here we review evidence suggesting that epigenetic therapeutics can deactivate immunosuppressive gene expression or reprogram tumor cells to activate antigen presentation mechanisms. In addition, the dysregulation of epigenetic mechanisms commonly observed in cancer may alter the immunogenicity of tumor cells and effectiveness of immunotherapies. Conclusions Therapeutics targeting epigenetic mechanisms may be helpful to counter immune evasion and improve the effectiveness of immunotherapies.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Chen Yao ◽  
Roby Joehanes ◽  
Rory Wilson ◽  
Toshiko Tanaka ◽  
Luigi Ferrucci ◽  
...  

Abstract Background DNA methylation is a key epigenetic modification that can directly affect gene regulation. DNA methylation is highly influenced by environmental factors such as cigarette smoking, which is causally related to chronic obstructive pulmonary disease (COPD) and lung cancer. To date, there have been few large-scale, combined analyses of DNA methylation and gene expression and their interrelations with lung diseases. Results We performed an epigenome-wide association study of whole blood gene expression in ~ 6000 individuals from four cohorts. We discovered and replicated numerous CpGs associated with the expression of cis genes within 500 kb of each CpG, with 148 to 1,741 cis CpG-transcript pairs identified across cohorts. We found that the closer a CpG resided to a transcription start site, the larger its effect size, and that 36% of cis CpG-transcript pairs share the same causal genetic variant. Mendelian randomization analyses revealed that hypomethylation and lower expression of CHRNA5, which encodes a smoking-related nicotinic receptor, are causally linked to increased risk of COPD and lung cancer. This putatively causal relationship was further validated in lung tissue data. Conclusions Our results provide a large and comprehensive association study of whole blood DNA methylation with gene expression. Expression platform differences rather than population differences are critical to the replication of cis CpG-transcript pairs. The low reproducibility of trans CpG-transcript pairs suggests that DNA methylation regulates nearby rather than remote gene expression. The putatively causal roles of methylation and expression of CHRNA5 in relation to COPD and lung cancer provide evidence for a mechanistic link between patterns of smoking-related epigenetic variation and lung diseases, and highlight potential therapeutic targets for lung diseases and smoking cessation.


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