title: Auto-regulation of the Sohlh1 gene by the SOHLH2/SOHLH1/SP1 complex: implications for early spermatogenesis and oogenesis.
abstract: Tissue-specific basic helix-loop-helix (bHLH) transcription factor proteins often play essential roles in cellular differentiation. The bHLH proteins SOHLH2 and SOHLH1 are expressed specifically in spermatogonia and oocytes and are required for early spermatogonial and oocyte differentiation. We previously reported that knocking out Sohlh2 causes defects in spermatogenesis and oogenesis similar to those in Sohlh1-null mice, and that Sohlh1 is downregulated in the gonads of Sohlh2-null mice. We also demonstrated that SOHLH2 and SOHLH1 can form a heterodimer. These observations led us to hypothesize that the SOHLH2/SOHLH1 heterodimer regulates the Sohlh1 promoter. Here, we show that SOHLH2 and SOHLH1 synergistically upregulate the Sohlh1 gene through E-boxes upstream of the Sohlh1 promoter. Interestingly, we identified an SP1-binding sequence, called a GC-box, adjacent to these E-boxes, and found that SOHLH1 could bind to SP1. Furthermore, chromatin-immunoprecipitation analysis using testes from mice on postnatal day 8 showed that SOHLH1 and SP1 bind to the Sohlh1 promoter region in vivo. Our findings suggest that an SOHLH2/SOHLH1/SP1 ternary complex autonomously and cooperatively regulates Sohlh1 gene transcription through juxtaposed E- and GC-boxes during early spermatogenesis and oogenesis.
authors.affiliation: Division of Stem Cell Regulation Research, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Toyoda
authors.affiliation: Division of Stem Cell Regulation Research, Osaka University Graduate School of Medicine, Osaka, Japan; Laboratory of Reproductive Engineering, the Institute of Experimental Animal Sciences, Osaka University Medical School, Osaka, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Yoshimura
authors.affiliation: Division of Stem Cell Regulation Research, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Mizuta
authors.affiliation: Division of Stem Cell Regulation Research, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Miyazaki
mesh_terms: D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D024721:E-Box Elements; D005260:Female; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism; D009866:Oogenesis / Q000235:genetics; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D055503:Protein Multimerization; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D013091:Spermatogenesis / Q000235:genetics; D015533:Transcriptional Activation
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D046912:Multiprotein Complexes; D016329:Sp1 Transcription Factor; C511466:Sohlh1 protein, mouse; C515516:Sohlh2 protein, mouse