Expression profile analysis in cells overexpressing DRPLA cDNA to explore the roles of DRPLAp as a transcriptional coregulator

Background: Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder caused by the unstable expansion of CAG repeats encoding polyglutamine stretches in DRPLA gene (ATN1). DRPLAp, the gene product of ATN1, is located in the nucleus and has been shown to function as a transcriptional coregulator. Its target genes, however, remain largely unknow. Aim: To elucidate the physiological functions of DRPLAp based on determination of the target genes regulated by wild-type DRPLAp. Methods: Using the cultured cells expressing wild-type full-length DRPLA cDNA (Q19) encoding DRPLAp under the control of the doxycycline (Dox)-On system, we searched for genes whose expression levels were regulated by wild-type DRPLAp (Q19). Results: On the basis of detailed RNA-seq analyses, we identified seven up-regulated genes and five down-regulated genes in Q19 cells. In gene ontology analysis, the up-regulated differentially expressed genes formed clusters featuring skeletal system morphogenesis, transcriptional regulation, and RNA metabolism, which is consistent with the recent report that the mutations in ATN1 lead to recognizable facial form and variable congenital anomalies. Conclusion: These findings support that DRPLAp may play a role as a transcriptional coregulator involved in the regulation of development.