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

Junjun Jiang; Nannan Zhang; Hiroshi Shiba; Liyuan Li; Zhao Wang

doi:10.1371/journal.pone.0075933

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.

Authors

Junjun Jiang¹, Nannan Zhang, Hiroshi Shiba, Liyuan Li, Zhao Wang

Affiliation

¹ MOE Key Laboratory of Protein Sciences, Department of Pharmacology, School of Medicine, Tsinghua University, Beijing, China.

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

Grants and funding

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.