SOHLH1 and SOHLH2 directly down-regulate STIMULATED BY RETINOIC ACID 8 (STRA8) expression

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 regula...

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Bibliographic Details
Published in:Cell cycle (Georgetown, Tex.) Tex.), 2015, Vol.14 (7), p.1036-1045
Main Authors: Desimio, M G, Campolo, F, Dolci, S, De Felici, M, Farini, D
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Base Sequence
Basic Helix-Loop-Helix Transcription Factors - physiology
Cell Differentiation
Down-Regulation
Gene Expression
Gene Silencing
HEK293 Cells
Humans
Male
Molecular Sequence Data
Promoter Regions, Genetic
Protein Binding
Spermatogonia - physiology
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Summary: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 KIT(+) 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 KIT(+) spermatogonia. We hypothesize that this novel negative activity of SOHLH1 and 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.
ISSN:1538-4101
1551-4005
DOI:10.1080/15384101.2015.1007721