Work

Peptidyl arginine deiminase 2 (Padi2) is expressed in Sertoli cells in a specific manner and regulated by SOX9 during testicular development

Year: 2018

Type: article

Abstract: Peptidyl arginine deiminases (PADIs) are enzymes that change the charge of proteins through citrullination. We recently foundPadi2was expressed exclusively in fetal Sertoli cells. In this study, we analyzed the transcriptional regulation ofPadi2and the role of PADI2 in testicular development. We showed SOX9 positively regulatedPadi2transcription and FOXL2 antagonized it in TM3 cells, a model of Sertoli cells. The responsive region to SOX9 and FOXL2 was identified within thePadi2sequence by reporter assay. In fetal testes fromSox9knockout (AMH-Cre:Sox9flox/flox) mice,Padi2expression was greatly reduced, indicating SOX9 regulatesPadi2 in vivo.In vitroanalysis using siRNA suggested PADI2 modified transcriptional regulation by SOX9. However,Padi2−/−XY mice were fertile and showed no apparent reproductive anomalies. Although, PADI2 is known as an epigenetic transcriptional regulator through H3 citrullination, no significant difference in H3 citrullination between wildtype andPadi2−/−XY gonads was observed. These results suggestPadi2is a novel gene involved in testis development that is specifically expressed in Sertoli cells through the regulation by SOX9 and FOXL2 and PADI2 supports regulation of target genes by SOX9. Analysis of thePadi2−/−XY phenotype suggested a redundant factor compensated for PADI2 function in testicular development.

Source: Scientific Reports

DOI: 10.1038/s41598-018-31376-8