Introduction: Skeletal muscle plasticity in exercise can be modulated by epigenomic events such as gene silencing, histone modifications and DNA methylation. In this context, our objective was to analyze the expression of genes associated with chromatin modifications in human muscle biopsies of vastus lateralis after a 20 week training program. Methods: Using data from DNA microarray experiments registered in the NCBI GEO DataSet database GSE117070, we calculated the Z ratio values as the criterion to evaluate the differential expression of genes associated with chromatin modification during aerobic training in skeletal muscle. Using the web interface GENEMANIA, we built a co-expression interaction network with the overexpressed genes. We compared Z-score values obtained from pre-trained and post-trained samples through nonparametric tests. Results: We found 10 overexpressed genes after the 20 week training program, namely, EZH1, KMT2A, KMT2D, KDM4C, KDM6A, CREBBP, HDAC10, HDAC4, DNMT3L, and H2AX. The most relevant biological processes obtained from the network included chromatin organization (FDR 9.04×10-9) and histone modification (FDR 9.04×10-9). Conclusions: In skeletal muscle, after aerobic training, there is overexpression of genes associated with the modification of the chromatin through alterations in histones and DNA, resulting in epigenetic transcriptional changes.