The myomiR-206 partecipate to muscle-regeneration by sculpting the chromatin through the down.regulation of the non-histone chromatin-associated protein High Mobility group protein 3 (Hmgb3)

MiR-206 is a muscle specific miRNA involved in muscle development and myogenesis. Importantly its function was mostly associated to muscle regeneration by the down-regulation of several target genes triggered during muscle repair (Pax7, Cx43 and Utrn). In order to better characterize the function of miR-206 in muscle remodelling, we induced acute muscle damage in control mice by injecting cardiotoxin (CTX) in the tibialis (TA) of c57bl mice. We isolated single muscle fiber from injected TA and quantified by absolute Realt-Time PCR (Q-PCR) the expression levels of miR-206. Furthermore in situ hybridization experiments on tissue slices of damaged TA were performed in order to localized miR-206. Data obtained highlighted the over-expression of miR-206 in newly formed and regenerating myofibers, demostrating the association of miR-206 with muscle regeneration. Furthermore, a target-gene prediction-analysis for miR-206 was performed by using 6 different computational algorithms (PITA, TargetScan, PicTar, ElMMo, miRDb and miRanda). Among the predicted target genes, we found the high mobility group box 3 (Hmgb3 or HMG4) which is a non-histone, chromatin-associated nuclear protein that interacts with transcription factors, enhancing the binding of these transcription factors to DNA and their transcriptional activity. Target validation and speculiar expression profile of miR-206 and Hmgb3 during myogenesis and muscle repair, demonstrate that miR-206 influence skeletal-muscle remodelling by sculpting the chromatin. These data established a role for miR-206 in the complex regulatory world of epigenetics. Future experiments will be performed in order to understand the function of Hmgb3 in skeletal muscle and myogenesi