The master regulator gene PRDM2 controls C2C12 myoblasts proliferation and Differentiation switch and PRDM4 and PRDM10 expression

The Positive Regulatory Domain (PRDM) protein family gene is involved in a spectrum variety of biological processes, including proliferation, differentiation and apoptosis: its member seem to be transcriptional regulators highly cell type and tissue peculiar, towards histones modifications or recruitment of specific interaction patters to modify the expression of target genes. In this study we analyzed the expression profile of different member of PRDM gene family focusing our attention on the role of PRDM2, PRDM4 and PRDM10 genes in mouse C2C12 cell line, during the differentiation of myoblasts into myotubes and speculate about the role of the protein Retinoblastoma protein-interacting zinc finger protein 1-RIZ1, coded by PRDM2 gene, as a regulator of the proliferation/differentiation switch. Results showed a reduction of PRDM2, PRDM4 and PRDM10 expression level during the commitment of the differentiation of myoblasts into myotubes. The RIZ1 silencing stimulated myoblasts differentiation, similar to the effect of serum deprivation on these cells, associated with an increase of Myogenin expression level, which is considered to be involved in the differentiation of myoblasts into multinucleated myotubes. As demonstrated by chromatin immunoprecipitation experiments, RIZ1 is associated with Myogenin promoter in proliferation condition and after 24h from differentiation induction, negatively controlling therefore Myogenin expression. Moreover RIZ1 silencing induced a reduction in PRDM4 and PRDM10 expression levels leaving us to speculate that the PRDM genes have a redundant role and they are hierarchically organized