Maintaining striated muscle identity and proper cardiac function depend on the contractile proteins that form the cardiomyocyte sarcomere, whose expression is regulated by transcriptional and epigenetic mechanisms. This regulation involves the Chd4/NuRD chromatin remodeling complex, which cooperates with transcription factors to regulate transcription. This master's thesis studies the role of microRNAs in this process.

process, analyzing whether the deregulation of its expression is related to the existence of differentially expressed transcripts in the heart of Chd4 knockout mice and the ThPOK transcription factor that may explain the arrhythmias, cardiomyopathies and sudden death observed in the mutant mice.

In this study, different web platforms and R packages were used, including mirnaQC and sRNAbench, for quality analysis, filtering, counting, and differential expression of sequenced miRNAs from wild-type, Chd4 knockout, and Chd4 and ThPOK double knockout mice. The results were compared with differentially expressed genes for these conditions, using multiMiR and miRTarVis for interaction definition and visualization. Finally, miRNA/mRNA interactions that could explain the observed phenotypes were defined through enrichment analysis using g:Profile, DAVID, and Enrichr.

This analysis demonstrates differences in miRNA expression across conditions, some with validated interactions with genes involved in muscle contraction, which could cause the phenotypes of the mice studied, such as the Atp1b4 and mmu-miR-149-5p pairs, Ryr1 and mmu-miR-378a-3p, or Kcnf1 and miR-335-3p pairs. The study also confirms that the upregulation of Sprr1a is related to a downregulation of mmu-miR-150, corroborating the results obtained by Dr. Gómez del Arco's team.

The results therefore indicate that Chd4 and ThPOK influence the expression of miRNAs that regulate the expression of genes that are part of pathways of interest in the mouse heart, explaining how a deregulation of these pathways could cause cardiac arrhythmias.

The work is available in the repository .