Journal
CELL CYCLE
Volume 14, Issue 7, Pages 1036-1045Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15384101.2015.1007721
Keywords
meiosis; SOHLH1; SOHLH2; spermatogonia; STRA8
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Funding
- Ministero dell'Istruzione, dell'Universita e della Ricerca Scientifica (PRIN, Italy) [2010C8ERKX_003]
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As the name implies, Stimulated by Retinoic Acid 8 is an early retinoic acid (RA) responsive gene pivotal for the beginning of meiosis in female and male germ cells. Its expression is strictly time-dependent and cell-specific (pre-meiotic germ cells) and likely requires a complex mechanism of regulation. In this study, we demonstrate a direct negative control of SOHLH1 and SOHLH2, 2 germ cell specific bHLH transcription factors, on Stra8 expression. We observed a negative correlation between STRA8 and SOHLH1 expression in prepuberal differentiating mouse KITC spermatogonia and found that SOHLH1 and SOHLH2 were able to directly and cooperatively repress STRA8 expression in cell lines in vitro through binding to its promoter. We also identified 2 canonical E-Box motives in the Stra8 promoter that mediated the negative regulation of SOHLH1 and SOHLH2 on these gene both in the cell lines and KITC spermatogonia. We hypothesize that this novel negative activity of SOHLH1and SOHLH2 in male cooperates with that of other transcription factors to coordinate spermatogonia differentiation and the RA-induced meiosis and in female ensures STRA8 down-regulation at mid-end stages of meiotic prophase I.
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