Identification of SEPTIN12 as a novel target of the androgen and estrogen receptors in human testicular cells

Pao-Lin Kuo, Jie Yun Tseng, Hau Inh Chen, Chia Yun Wu, Hany A. Omar, Chia-Yih Wang, Han Yi Cheng, Chao Chin Hsu, Tzu-Fun Fu, Yen Ni Teng

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalBiochimie
Volume158
DOIs
Publication statusPublished - 2019 Mar 1

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Androgen Receptors
Estrogen Receptors
Genes
Dihydrotestosterone
Genetic Promoter Regions
Testis
Binding Sites
Hormones
Endocrine Disruptors
Sperm Motility
Chromatin Immunoprecipitation
Transcription Initiation Site
Spermatogenesis
Bioinformatics
Computational Biology
Polymorphism
Androgens
Chromatin
Single Nucleotide Polymorphism
Estradiol

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Kuo, Pao-Lin ; Tseng, Jie Yun ; Chen, Hau Inh ; Wu, Chia Yun ; Omar, Hany A. ; Wang, Chia-Yih ; Cheng, Han Yi ; Hsu, Chao Chin ; Fu, Tzu-Fun ; Teng, Yen Ni. / Identification of SEPTIN12 as a novel target of the androgen and estrogen receptors in human testicular cells. In: Biochimie. 2019 ; Vol. 158. pp. 1-9.
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abstract = "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.",
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Identification of SEPTIN12 as a novel target of the androgen and estrogen receptors in human testicular cells. / Kuo, Pao-Lin; Tseng, Jie Yun; Chen, Hau Inh; Wu, Chia Yun; Omar, Hany A.; Wang, Chia-Yih; Cheng, Han Yi; Hsu, Chao Chin; Fu, Tzu-Fun; Teng, Yen Ni.

In: Biochimie, Vol. 158, 01.03.2019, p. 1-9.

Research output: Contribution to journalArticle

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AU - Kuo, Pao-Lin

AU - Tseng, Jie Yun

AU - Chen, Hau Inh

AU - Wu, Chia Yun

AU - Omar, Hany A.

AU - Wang, Chia-Yih

AU - Cheng, Han Yi

AU - Hsu, Chao Chin

AU - Fu, Tzu-Fun

AU - Teng, Yen Ni

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Y1 - 2019/3/1

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AB - 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.

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