An integrative analysis reveals coordinated reprogramming of the epigenome and the tran... - 0 views
-
contribution to the training response of the epigenome as a mediator between genes and environment
-
Differential DNA methylation was predominantly observed in enhancers, gene bodies and intergenic regions and less in CpG islands or promoters
-
highly consistent and associated modifications in methylation and expression, concordant with observed health-enhancing phenotypic adaptations, are induced by a physiological stimulus
- ...34 more annotations...
-
The health benefits following exercise training are elicited by gene expression changes in skeletal muscle, which are fundamental to the remodeling process
-
there is increasing evidence that more short-term environmental factors can influence DNA methylation
-
dietary factors have the potency to alter the degree of DNA methylation in different tissues, 9,10 including skeletal muscle
-
In one study, a single bout of endurance-type exercise was shown to affect methylation at a few promoter CpG sites
-
In the context of diabetes, exercise training has been shown to affect genome-wide methylation pattern in skeletal muscle,13 as well as in adipose tissue.
-
physiological stressors can indeed affect DNA methylation
-
training intervention reshapes the epigenome and induces significant changes in DNA methylation
-
the findings from this tightly controlled human study strongly suggest that the regulation and maintenance of exercise training adaptation is to a large degree associated to epigenetic changes, especially in regulatory enhancer regions
-
Endurance training [after training (T2) vs. before training (T1)] induced significant (false discovery rate, FDR< 0.05) methylation changes at 4919 sites across the genome in the trained leg
-
identified 4076 differentially expressed genes
-
a complementary approach revealed that over 600 CpG sites correlated to the increase in citrate synthase activity, an objective measure of training response (Figure S4 and Dataset S14). This might imply that some of these sites could influence the degree of training response.
-
As expected by a physiological environmental trigger on adult tissue, the observed effect size on DNA methylation was small in comparison to disease states such as cancer
-
a preferential localization outside of CpG Islands/Shelves/Shores
-
endurance training especially influences enhancers
-
negative correlation was more prominent for probes in promoter/5′UTR/1st exon regions, while gene bodies had a stronger peak of positive correlation
-
The significant changes in DNA methylation, that primarily occurred in enhancer regions, were to a large extent associated with relevant changes in gene expression
-
The main findings of this study were that 3 months of endurance training in healthy human volunteers induced significant methylation changes at almost 5000 sites across the genome and significant differential expression of approximately 4000 genes
-
DMPs that increased in methylation were mainly associated to structural remodeling of the muscle and glucose metabolism, while the DMPs with decreased methylation were associated to inflammatory/immunological processes and transcriptional regulation
-
This suggests that the changes in methylation seen with training were not a random effect across the genome but rather a controlled process that likely contributes to skeletal muscle adaptation to endurance training
-
Correlation of the changes in DNA methylation to the changes in gene expression showed that the majority of significant methylation/expression pairs were found in the groups representing either increases in expression with a concomitant decrease in methylation or vice versa
-
The fraction of genes showing both significant decrease in methylation and upregulation was 7.5% of the DEGs or 2.3% of all genes detected in muscle tissue with at least one measured DNA methylation position. Correspondingly, 7.0% of the DEGs or 2.1% of all genes showed both significant increase in methylation and downregulation
-
we show that DNA methylation changes are associated to gene expression changes in roughly 20% of unique genes that significantly changed with training
-
Examples of structural genes include COL4A1, COL4A2 and LAMA4. These genes have also been identified as important for differences in responsiveness to endurance training
-
methylation status could be part of the mechanism behind variable training response
-
Among the metabolic genes, MDH1 catalyzes the reversible oxidation of malate to oxaloacetate, utilizing the NAD/NADH cofactor system in the citric acid cycle and NDUFA8 plays an important role in transferring electrons from NADH to the respiratory chain
-
PPP1R12A,
-
In the present study, methylation predominantly changed in enhancer regions with enrichment for binding motifs for different transcription factors suggesting that enhancer methylation may be highly relevant also in exercise biology
-
Of special interest in the biology of endurance training may be that MRFs, through binding to the PGC-1α core promoter, can regulate this well-studied co-factor for mitochondrial biogenesis
-
That endurance training led to an increased methylation in enhancer regions containing motifs for the MRFs and MEFs is somewhat counterintuitive since it should lead to the repression of the action of the above discussed transcription factors
-
decrease with training in this study, including CDCH15, MYH3, TNNT2, RYR1 and SH3GLB1
-
expression of MEF2A itself decreased with training
-
this study demonstrates that the transcriptional alterations in skeletal muscle in response to a long-term endurance exercise intervention are coupled to DNA methylation changes
-
We suggest that the training-induced coordinated epigenetic reprogramming mainly targets enhancer regions, thus contributing to differences in individual response to lifestyle interventions
-
a physiological health-enhancing stimulus can induce highly consistent modifications in DNA methylation that are associated to gene expression changes concordant with observed phenotypic adaptations
-
Exercise alters gene expression via methylation--the power of epigenetics. Interestingly, the majority of the methylation was outside the CPG island regions. This 3 month study found methylation of 5,000 sites across the genome resulting in altered expression of apps 4,000 genes. The altered muscle changes of the endurance training was linked to DNA methylation changes.
