## 7 Discussion and Conclusions
The overexpression of HDAC4 and HDAC10 in our study may be associated with metabolic-type enzymatic processes, which normally occur in the cytoplasm or mitochondria; the enzymes involved are pyruvate dehydrogenase complex (PDHC), lactate dehydrogenase (LHD), alanine aminotransferase (ALT), and succinate dehydrogenase (SDH) [29]. These enzymes supply metabolites that regulate the activity of chromatin-modifying or transcriptional regulatory enzymes to regulate gene expression and chromatin structure. One of those metabolic products is lactate; this behaves as an endogenous inhibitory metabolite of HDAC that targets the histone 4 complex [30], acetylating histone marks and inducing the overexpression found in this study. This increase in lactate concentration occurs during training when the athlete is subjected to an incremental test measured by oxygen consumption [31]. The changes presented in the training program induced the overexpression of enzymes such as DNMT3L that regulates CpG methylation and enzymes such as EZH1 that modulate trimethylation at lysine residues 4, 27, and 36 of histone H3. During this type of training program, the availability of the ATP used increases, in association with the changes generated in the mitochondria by the expression of PGC1\(\alpha\). Enzymes such as methionine adenosyl transferase (MAT) use ATP during methylation reactions [32], which are carried out by enzymes that regulate the methylation marks of DNA in lysine residues of histones and CpG islands. The training program established for this study, with incremental intensity from 55% to 75% of VO\({}_{\text{2 max}}\), provides solid evidence supporting the hypothesis that, in skeletal muscle, there is overexpression of genes associated with the modification of chromatin through alterations in histones and DNA, resulting in epigenetic transcriptional changes. The following are available online at [[https://www.mdpi.com/article/10.3390/app12031159/s1](https://www.mdpi.com/article/10.3390/app12031159/s1)]([https://www.mdpi.com/article/10.3390/app12031159/s1](https://www.mdpi.com/article/10.3390/app12031159/s1)): Table S1. Description of overexpressed genes associated with chromatin modifications in skeletal muscle included in the present study. [PERSON], [PERSON] and [PERSON] performed data acquisition and information processing; [PERSON], [PERSON], [PERSON] and [PERSON] wrote the introduction and the methods; [PERSON], [PERSON] and [PERSON] wrote the results, discussion, and conclusions. All authors have read and agreed to the published version of the manuscript. The APC for this research was funded by the Directorate General of Research (Direccion General de Investigaciones) of the Universidad Santiago de Cali. This research has been funded by the vice-rectory of research at the Universidad del Valle through the scholarship 119-2019. **Informed Consent Statement:** Not applicable. Data Availability Statement:DNA microarray experiment whose registration code in the GEO database is GSE117070. ([[https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE117070](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE117070)]([https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE117070](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE117070)) accessed on 17 May 2019). To the Universidad Santiago de Cali and the Universidad del Valle. Nonne of the authors presents a conflict of interest.