Spermatogenesis associated 4 promotes Sertoli cell proliferation modulated negatively by regulatory factor X1

PLoS One. 2013 Oct 11;8(10):e75933. doi: 10.1371/journal.pone.0075933. eCollection 2013.

Abstract

Spermatogenesis associated 4 (Spata4), a testis-specific and CpG island associated gene, is involved in regulating cell proliferation, differentiation and apoptosis. To obtain insight into the role of Spata4 in cell cycling control, we characterized the promoter region of Spata4 and investigated its transcriptional regulation mechanism. The Spata4 promoter is unidirectional transcribed and possesses multiple transcription start sites. Moreover, we present evidence that regulatory factor X1 (RFX1) could bind the typical 14-bp cis-elements of Spata4 promoter, modulate transcriptional activity and endogenous expression of Spata4, and further regulate the proliferation of Sertoli cells. Overexpression of RFX1 was shown to down-regulate both the promoter activity and mRNA expression of Spata4, whereas knockdown of RFX1 demonstrated the opposite effects. Our studies provide insight into Spata4 gene regulation and imply the potential role of RFX1 in growth of Sertoli cells. RFX1 may have negative effect on cell proliferation of Sertoli cells via modulating Spata4 expression levels by binding the conserved 14-bp cis-elements of Spata4 promoter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Conserved Sequence
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Developmental*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • Proteins / genetics*
  • Proteins / metabolism
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Regulatory Factor X Transcription Factors
  • Regulatory Factor X1
  • Sertoli Cells / cytology
  • Sertoli Cells / metabolism*
  • Spermatogenesis / genetics*
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • DNA-Binding Proteins
  • Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • Regulatory Factor X Transcription Factors
  • Regulatory Factor X1
  • Rfx1 protein, mouse
  • SPATA4 protein, mouse
  • Transcription Factors

Grant support

This work was financially supported by the National Basic Research Program (973 Project) of China (Nos. 2007CB507406, 2013CB530802) and the National Natural Science Foundation of China (No. 81270425). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.