SEPTIN12 (SEPT12) is a testis-enriched gene that is downregulated in the testis of infertile men with severe spermatogenic defects. While SEPT12 is involved in spermatogenic failure and sperm motility disorder, SEPT12 transcriptional regulation is still unknown. Here we report the promoter region of SEPT12 as a 245 bp segment upstream of the transcription start site. One androgen receptor (AR) and two estrogen receptor α (ERα) binding sites in this region were initially identified by bioinformatics prediction and confirmed by chromatin immunoprecipitation assay. Truncated ERα or AR binding sites decreased the promoter activity, which indicated that the ERα and AR are essential for the SEPT12 promoter. On the other hand, the promoter activity was enhanced by the treatment with 17β-estradiol (E2) and 5α-dihydrotestosterone (5α-DHT). Thus, one androgen and two estrogen hormone responsive elements located in the promoter of SEPT12 gene can regulate SEPT12 expression.

Two single nucleotide polymorphisms (SNPs), rs759992 T > C and rs3827527 C > T, were observed in the SEPT12 gene promoter region and were able to decrease the promoter activity. In conclusion, the current work identified the promoter of the human SEPT12 gene and provided key evidence about its transcriptional regulation via E2 and 5α-DHT. Since SEPT12 has an important role in spermatogenesis, SEPT12 expression analysis can be developed as a potential tool for the assessment of environmental or food pollution by hormones or for the evaluation of the risk of endocrine-disrupting chemicals (EDCs) in general.

SEPTIN12 (SEPT12)是一种富含睾丸的基因，在患有严重生精缺陷的不育男性的睾丸中下调。虽然SEPT12与生精功能障碍和精子活力障碍有关，但SEPT12转录调控仍然未知。在这里，我们将SEPT12的启动子区域报告为转录起始位点上游的 245 bp 片段。该区域中的一个雄激素受体 (AR) 和两个雌激素受体α (ERα) 结合位点最初通过生物信息学预测确定，并通过染色质免疫沉淀试验得到证实。截短的 ERα 或 AR 结合位点降低了启动子活性，这表明 ERα 和 AR 对于SEPT12发起人。另一方面，17β-雌二醇（E2）和5α-二氢睾酮（5α-DHT）处理增强了启动子活性。因此，位于SEPT12基因启动子中的一个雄激素和两个雌激素响应元件可以调节SEPT12 的表达。

在SEPT12基因启动子区域观察到两个单核苷酸多态性 (SNP)，rs759992 T > C 和 rs3827527 C > T，并且能够降低启动子活性。总之，目前的工作确定了人类SEPT12基因的启动子，并为其通过 E2 和 5α-DHT 的转录调控提供了关键证据。由于SEPT1 2 在精子发生中具有重要作用，因此可以将SEPT12表达分析开发为一种潜在的工具，用于评估激素对环境或食物的污染，或用于评估一般的内分泌干扰化学物质 (EDC) 的风险。