## 7 Discussion and Conclusions  
In the present study, our objective was to perform a bioinformatic analysis of the differential expression of genes in muscle associated with chromatin modification from biopsy samples of the vastus lateralis of the quadriceps muscle in humans who were included in a 20 week aerobic exercise program. The original study that provided the source data for this analysis was presented by [PERSON] in 1995, the HERITAGE family study, which presented the methodology describing the role of the genotype in the cardiovascular, metabolic, and hormonal responses to aerobic exercise training, in 90 Caucasian families and 40 African American families with both parents and three or more biological adult descendants [21]. On the contrary, in our article, we did not focus the objectives, design, and measurement protocol. Moreover, in the study by [PERSON] et al. [23], which used the same source data, the authors found that knockdown of the mTOR-independent factor Eif6, which we predicted to be a key regulator of this process, affects mitochondrial respiration efficiency, ROS production, and exercise performance. Conversely, our results were focused on the genes associated with chromatin changes due to aerobic training. The overexpressed genes found in the present study corresponded to EZH1, KMT2A, KMT2D, KDM4C, KDM6A, CREBBP, HDAC10, HDAC4, DNMT3L, and H2 AX. All of them were previously reported to be important in chromatin organization and histone modification, including histone methylation in skeletal muscle described by the biological processes in Table 2, allowing changes in the sarcomere specifically in the thin actin filament and reshaping the cell to a type of muscle fiber that adjusts to the needs of training, as explained by [PERSON] et al. [24]. For this reason, any dysregulation of these genes can affect their own functions and those of associated genes. Our results correlate with the study by [PERSON] et al. [25] which analyzed the impact of exercise on global histone modifications leading to transcriptional activation and chromatin remodeling in human skeletal muscle samples. The authors found that, during exercise, two histone deacetylase activity (HDAC) proteins were exported from the nucleus of the cells, not allowing them to accomplish their function as transcriptional repressors. In addition, [PERSON] et al. [26] studied the responses of histone alterations to resistance exercise in skeletal muscle in relation to resistance training; they found a significant upregulation  
Figure 3: Principal component analysis of post-training samples with the overexpressed genes found in this study shown as red dots. of the distribution of acetylated histone 3 (H3 Acet3), monomethylated H3 in lysine 4 (H3-threeMetK4), and trimethylated in lysine 27 (H3-threeMetK27). However, in our study, we found overexpression of lysine methyltransferase KMT2A and KMT2D, which are mainly responsible for the methyltransferase activity in lysine 4 of histone H3 (H3 MetK4). During muscle adaptations to resistance or aerobic training, the isoforms of myofibrillar proteins most frequently change in order to facilitate the entry of calcium during muscle relaxation; among these proteins are the heavy chain of myosin (MYH), the thin actin filaments, the troponin/tropomyosin complex, and even proteins of the sarcoplasmic and mitochondrial reticulum [27, 28]. Previous reports showed the exercise-induced transcription of GLUT4 in skeletal muscle through the deactivation of HDAC4/5, whereby suppressing the activity of HDAC4 led to an increase in the expression of GLUT4 during resistance training that started at 75% of VO\({}_{\text{2 max}}\); however, in our study, resistance training started at 55% of VO\({}_{\text{2 max}}\), implicating the overexpression of HDAC4 and HDAC10. For this reason, glucose that enters through GLUT becomes the source of energy during resistance exercise, modifying performance and metabolic flow through intensity and total workload.