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SOHLH1 and SOHLH2 directly down-regulate STIMULATED BY RETINOIC ACID 8 (STRA8) expression
M G Desimio1, F Campolo, S Dolci
1a Department of Biomedicine ; Section of Histology and Embryology ; University of "Tor Vergata" ; Rome , Italy.
Cell Cycle (Georgetown, Tex.)
|January 21, 2015
Summary
Germ cell transcription factors SOHLH1 and SOHLH2 directly repress Stra8 expression, a key gene for meiosis initiation. This finding reveals a novel regulatory mechanism coordinating germ cell differentiation and the onset of meiosis.
Area of Science:
- Reproductive Biology
- Molecular Biology
- Genetics
Background:
- Stimulated by Retinoic Acid 8 (Stra8) is a critical gene initiating meiosis in germ cells.
- Stra8 expression is tightly regulated in a time- and cell-specific manner.
- The precise regulatory mechanisms controlling Stra8 expression remain incompletely understood.
Purpose of the Study:
- To investigate the role of germ cell-specific bHLH transcription factors SOHLH1 and SOHLH2 in regulating Stra8 expression.
- To elucidate the mechanism by which SOHLH1 and SOHLH2 control Stra8 transcription.
Main Methods:
- Analysis of gene expression correlation in mouse spermatogonia.
- In vitro repression assays using cell lines with Stra8 promoter constructs.
- Identification of transcription factor binding sites (E-boxes) in the Stra8 promoter.
Main Results:
- A negative correlation was observed between STRA8 and SOHLH1 expression in differentiating mouse spermatogonia.
- SOHLH1 and SOHLH2 cooperatively repressed Stra8 expression in vitro by binding to its promoter.
- Two canonical E-Box motifs in the Stra8 promoter were identified as crucial for SOHLH1/S2-mediated repression.
Conclusions:
- SOHLH1 and SOHLH2 directly and negatively regulate Stra8 expression.
- This novel regulatory pathway involving SOHLH1/S2 and E-boxes is essential for coordinating spermatogonia differentiation and RA-induced meiosis.
- The findings suggest a role for this mechanism in ensuring proper Stra8 down-regulation during later stages of meiotic prophase I in females.
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