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.
Highlights
Transcriptional regulation is essential for cellular differentiation
Immunoprecipitation-assay bands indicating homodimerization were detected for both SOHLH2 (Figure 1C, lane 1) and SOHLH1 (Figure 1D, lane 1)
We reported that abnormalities in the testes and ovaries of Sohlh2-null mice are similar to those seen in Sohlh1-null mice, and that Sohlh1 transcription is downregulated in the gonads of Sohlh2-null mice [6]
Summary
Transcriptional regulation is essential for cellular differentiation. Previous studies have demonstrated that a number of transcriptional factors play important roles in early spermatogenesis and oogenesis [1,2]. The Sohlh transcript is upregulated shortly after birth, and the SOHLH2 protein is expressed in the adult testis by a portion of As spermatogonia throughout differentiation [6]. The Sohlh transcript is upregulated before birth [6], and its protein is expressed in primordial through primary oocytes in the ovary [3,6]. The Sohlh and Sohlh expression patterns are similar, the Sohlh transcript is upregulated following Sohlh expression in both early spermatogenesis and oogenesis [6]. The SOHLH1 protein is expressed by Aal spermatogonia throughout differentiation [3] Since both male and female Sohlh2- and Sohlh1null mice are infertile, and these mice have similar abnormalities in gonad histology and gene expression patterns, Sohlh may be upstream to Sohlh in the gene regulatory hierarchy
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