title: SOHLH1 and SOHLH2 directly down-regulate STIMULATED BY RETINOIC ACID 8 (STRA8) expression.
abstract: 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.
authors.affiliation: a Department of Biomedicine ; Section of Histology and Embryology ; University of "Tor Vergata" ; Rome , Italy.
authors.forename: M G
authors.initials: MG
authors.lastname: Desimio
authors.forename: F
authors.initials: F
authors.lastname: Campolo
authors.forename: S
authors.initials: S
authors.lastname: Dolci
authors.forename: M
authors.initials: M
authors.lastname: De Felici
authors.forename: D
authors.initials: D
authors.lastname: Farini
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology*; D002454:Cell Differentiation; D015536:Down-Regulation; D015870:Gene Expression; D020868:Gene Silencing; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D013093:Spermatogonia / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051792:Basic Helix-Loop-Helix Proteins; C511466:Sohlh1 protein, mouse; C515516:Sohlh2 protein, mouse; C102019:Stra8 protein, mouse
keywords: ChIP, chromatin immunoprecipitation; EC, Embyonal Carcinoma; PGC, primordial germ cell; RA, retinoic acid; RARE, Retinoic Acid Response Element; SOHLH1; SOHLH2; STRA8; STRA8, Stimulated by Retinoic Acid 8; TF, transcription factor; dpc, days post coitum; dpp, days postpartum; meiosis; spermatogonia