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| Status |
Public on Jan 21, 2021 |
| Title |
The comparative methylome and transcriptome after change of direction compared to straight line running exercise in human skeletal muscle |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by array
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| Summary |
The methylome and transcriptome signatures following exercise that are physiologically and metabolically relevant to sporting contexts such as team sports or health prescription scenarios (e.g. high intensity interval training/HIIT) has not been investigated. To explore this, we performed two different sport/exercise relevant high-intensity running protocols in 5 male sport team members using a repeated measures design of: 1) Change of direction (COD) versus; 2) straight line (ST) exercise with a wash-out period of at least 2 weeks between trials. Skeletal muscle biopsies collected from the vastus lateralis 30 minutes and 24 hours post exercise, were assayed using 850K methylation arrays and a comparative analysis with recent (subject-unmatched) sprint and acute aerobic exercise meta-analysis transcriptomes was performed. Despite COD and ST exercise being matched for classically defined intensity measures (speed x distance and number of accelerations/decelerations), COD exercise elicited greater movement (GPS-Playerload), physiological (HR), metabolic (lactate) as well as central and peripheral (differential RPE) measures compared with ST exercise, suggesting COD exercise evoked a higher exercise intensity. The exercise response alone across both conditions evoked extensive alterations in the methylome 30 mins and 24 hrs post exercise, particularly in MAPK, AMPK and axon guidance pathways. COD evoked a considerably greater hypomethylated signature across the genome compared with ST exercise, particularly at 30 minutes post exercise, enriched in: Protein binding, MAPK, AMPK, insulin, and axon guidance pathways. Comparative methylome analysis with sprint running transcriptomes identified considerable overlap, with 49% of genes that were altered at the expression level also differentially methylated after COD exercise. After differential methylated region analysis, we observed that VEGFA and its downstream nuclear transcription factor, NR4A1 had enriched hypomethylation within their promoter regions. VEGFA and NR4A1 were also significantly upregulated in the sprint transcriptome and meta-analysis of exercise transcriptomes. We confirmed increased gene expression of VEGFA, and considerably larger increases in the expression of canonical metabolic genes, PPARGC1A (that encodes PGC1-α) and NR4A3 in COD vs. ST exercise. Overall, we demonstrate that increased physiological/metabolic load via change of direction exercise in human skeletal muscle evokes considerable epigenetic modifications that are associated with changes in expression of genes responsible for adaptation to exercise.
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| Overall design |
A within-subject design conducted in young adult male humans. Each participant (1-3) underwent two running trials separated by a minimum of 2 weeks. Trial 1) Change of direction (COD) versus; Trial 2) straight line (ST) running exercise. Skeletal muscle biopsies were collected from the vastus lateralis muscle at baseline (at rest pre-exercise under overnight fasted conditions) as well as after 30 minutes and 24 hours post exercise in both trials. These samples were assayed using 850K Illumina EPIC methylation arrays and a comparative analysis with recent (subject-unmatched) sprint and acute aerobic exercise meta-analysis transcriptomes. Despite COD and ST exercise being matched for classically defined intensity measures (speed x distance and number of accelerations/decelerations), COD exercise elicited greater movement (GPS-Playerload), physiological (HR), metabolic (lactate) as well as central and peripheral (differential RPE) measures compared with ST exercise, suggesting COD exercise evoked a higher exercise intensity or ‘player-loading’. Therefore, the samples provided an opportunity to assess differences in DNA methylation across the genome following running exercise that evoked differential exercise intensities/playload in a model that was physiologically and metabolically relevant to sporting contexts such as team sports or health prescription scenarios (e.g. high intensity interval training/HIIT). Note - Participant 1 had their methylome profiled at baseline (pre-exercise under rested conditions) prior to both trials (COD & ST) separated by at least two weeks. These 2 baseline biopsies in the same participant were taken under the same conditions (baseline/rest/overnight fast) before each trial and demonstrated little variation in methylome profiles. Therefore, for the remaining participants (2 & 3) due to the reason above and because this was a within-subject trial, the baseline (pre-exercise/rested) sample for the first trial undertaken only (COD trial) was used as the baseline sample in downstream analysis. Hence why participants 1-3 have baseline, 30 minute and 24 hr samples for their COD trial and participants 2 & 3 only have 30 minute and 24 hr samples designated for their ST trial.
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| Contributor(s) |
Sharples AP |
| Citation(s) |
33679435 |
| Submission date |
Nov 27, 2020 |
| Last update date |
Apr 22, 2021 |
| Contact name |
Adam P Sharples |
| E-mail(s) |
a.p.sharples@googlemail.com
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| Phone |
+447812732670
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| Organization name |
Norwegian School of Sport Sciences
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| Department |
Institute for Physical Performance
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| Lab |
Dr Adam P Sharples
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| Street address |
220 Sognsveien
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| City |
Oslo |
| ZIP/Postal code |
0863 |
| Country |
Norway |
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| Platforms (1) |
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| Samples (16)
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| GSM4948519 |
methylation_participant 1_Change of Direction (COD)_Baseline |
| GSM4948520 |
methylation_participant 1_Change of Direction (COD)_Post |
| GSM4948521 |
methylation_participant 1_Change of Direction (COD)_24 h |
| GSM4948522 |
methylation_participant 2_Change of Direction (COD)_Baseline |
| GSM4948523 |
methylation_participant 2_Change of Direction (COD)_Post |
| GSM4948524 |
methylation_participant 2_Change of Direction (COD)_24 h |
| GSM4948525 |
methylation_participant 3_Change of Direction (COD)_Baseline |
| GSM4948526 |
methylation_participant 3_Change of Direction (COD)_Post |
| GSM4948527 |
methylation_participant 3_Change of Direction (COD)_24 h |
| GSM4948528 |
methylation_participant 1_Straight (ST)_Baseline |
| GSM4948529 |
methylation_participant 1_Straight (ST)_Post |
| GSM4948530 |
methylation_participant 1_Straight (ST)_24 h |
| GSM4948531 |
methylation_participant 2_Straight (ST)_24 h |
| GSM4948532 |
methylation_participant 3_Straight (ST)_Post |
| GSM4948533 |
methylation_participant 3_Straight (ST)_24 h |
| GSM4948534 |
methylation_participant 2_Straight (ST)_Post |
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| Relations |
| BioProject |
PRJNA681250 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE162288_NORMALISED_MASTER_matrix_signal_intensities_transpose_transpose.txt.gz |
85.9 Mb |
(ftp)(http) |
TXT |
| GSE162288_RAW.tar |
161.2 Mb |
(http)(custom) |
TAR |
| Processed data included within Sample table |
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