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

BMC Mol Biol. 2017 Jan 31;18(1):2. doi: 10.1186/s12867-017-0082-3.

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.

Keywords: Central apparatus; Cilia; S-SOX5; SPAG16L; Transcriptional regulation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Line
  • Humans
  • Microtubule-Associated Proteins / genetics*
  • Mutation
  • Promoter Regions, Genetic
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA Interference
  • RNA, Messenger / genetics
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / metabolism
  • SOXD Transcription Factors / genetics
  • SOXD Transcription Factors / metabolism*
  • Transcriptional Activation*

Substances

  • Microtubule-Associated Proteins
  • Protein Isoforms
  • RNA, Messenger
  • SOX5 protein, human
  • SOXD Transcription Factors
  • SPAG16 protein, human