Crosstalk Between the Centrosomal Protein AKNA and Epigenetic Modifiers Regulate Stemness During Neuronal Development

Abstract

Centrosomal protein AKNA plays an important role in neurogenesis during developmental processes. It was reported that AKNA has dual role, it can act as a structural protein as well as a transcription factor in context dependent manner. How AKAN acts as a transcription factor is yet to be resolved. In our study we have found that AKNA is upregulated in both stemness and differentiation in neuroblastoma cells. As we have found that in absence of AKNA protein, stemness markers are downregulated. So, we speculated that it might act as a transcription factor for maintaining stemness. Further we have studied the epigenetic cooperation between AKNA and epigenetic modifiers. From chromatin immunoprecipitation experiments, we have found that H3K27me3 is an important target for this protein to activate stemness markers. From this study we have prove that AKAN is necessary for recruitment of epigenetic modifiers by physical interactions like KDM6B in stemness markers promoter to regulate gene expression and maintaining neuronal stem cell properties. OAC1 and retinoic acid were used as a inducer of stemness and differentiation respectively in this study.