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PLoS One. 2018 Oct 31;13(10):e0205744. doi: 10.1371/journal.pone.0205744. eCollection 2018.

Regulation of CATSPER1 expression by the testis-determining gene SRY.

Author information

1
Unidad de Investigación Médica en Medicina Reproductiva, Hospital de Gineco- Obstetricia No. 4 Luis Castelazo Ayala, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, México.
2
Unidad de Investigación Médica en Inmunología e Infectología, Centro Médico Nacional, La Raza, IMSS, Ciudad de México, México.
3
Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (Cinvestav-IPN), Ciudad de México, México.
4
Departamento de Farmacogenómica, Instituto Nacional de Medicina Genómica (INMEGEN), Ciudad de México, México.
5
Departamento de Genética y Biología Molecular, Cinvestav-IPN, Ciudad de México, México.

Abstract

CATSPER1 gene encodes a pore-forming and pH-sensing subunit of the CatSper Ca2+- permeable channel, a protein in the flagellum essential for sperm hyperactivation. Previous studies have shown that the murine Catsper1 gene promoter is regulated by different Sox proteins. Likewise, it is acknowledged that the human CATSPER1 gene promoter sequence is enriched in potential interaction sites for the sex-determining region Y gene (SRY), which suggest a novel regulatory transcriptional mechanism for CatSper1 channel expression. Therefore, in this work, we sought to determine whether the human CATSPER1 gene expression is regulated by the SRY transcription factor. To this end, a series of deletions and mutations were introduced in the wild- type CATSPER1 gene promoter to eliminate the SRY sites, and the different constructs were tested for their ability to activate transcription in human embryonic kidney and murine spermatogonial germ cell lines (HEK-293 and GC1-spg, respectively) using luciferase assays. In addition, by using a strategy that combines electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) we investigated whether the CATSPER1 gene expression is regulated by the SRY transcription factor both in vitro and in vivo. Our results show that the transcriptional factor SRY specifically binds to different sites in the promoter sequence and has the ability to control CATSPER1 gene transcription.

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