Transcriptional regulation of human sperm-associated antigen 16 gene by S-SOX5

Abstract

Background: The mammalian sperm-associated antigen 16 gene (Spag16) uses alternative promoters to produce two major transcript isoforms (Spag16L and Spag16S) and encode proteins that are involved in the cilia/flagella formation and motility. In silico analysis of both mouse and human SPAG16L promoters reveals the existence of multiple putative SOX5 binding sites. Given that the SOX5 gene encodes a 48-kDa transcription factor (S-SOX5) and the presence of putative SOX5 binding sites at the SPAG16L promoter, regulation of SPAG16L expression by S-SOX5 was studied in the present work. Results: S-SOX5 activated human SPAG16L promoter activity in the human bronchial epithelia cell line BEAS-2B cells. Mutation of S-SOX5 binding sites abolished the stimulatory effect. Overexpression of S-SOX5 resulted in a significant increase in the abundance of SPAG16L transcripts whereas silencing of S-SOX5 by RNAi largely reduced the SPAG16L expression. Chromatin immunoprecipitation assays showed that S-SOX5 directly interacts with the SPAG16L promoter. Conclusion: S-SOX5 regulates transcription of human SPAG16L gene via directly binding to the promoter of SPAG16L. It has been reported that expression of sperm-associated antigen 6 (SPAG6), encoding another axonemal protein, is activated by S-SOX5. Therefore, S-SOX5 may regulate formation of motile cilia/flagella through globally mediating expression of genes encoding axonemal proteins.