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Arch Med Res. 2018 Apr;49(3):135-146. doi: 10.1016/j.arcmed.2018.06.004. Epub 2018 Jul 13.

Human CATSPER1 Promoter Is Regulated by CREB1 and CREMτ Transcriptional Factors In Vitro.

Author information

1
Unidad de Investigación Médica en Inmunología e Infectología, Centro Médico Nacional, La Raza, Instituto Mexicano del Seguro Social, Ciudad de México, México. Electronic address: naoviedoa@yahoo.com.mx.
2
Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de México, México.
3
Unidad de Investigación Médica en Inmunología e Infectología, Centro Médico Nacional, La Raza, Instituto Mexicano del Seguro Social, Ciudad de México, México.
4
Universidad Autónoma Metropolitana, Unidad Cuajimalpa, Ciudad de México, México.
5
Unidad de Investigación Médica en Inmunología e Infectología, Centro Médico Nacional, La Raza, Instituto Mexicano del Seguro Social, Ciudad de México, México. Electronic address: bekkermendez@yahoo.com.

Abstract

BACKGROUND:

The CATSPER1 gene encodes a CATSPER channel protein that selectively permeates Ca2+ ions, and CATSPER expression in sperm is essential for flagellum hyperactivation and, thus, male fertility. Little is known regarding the transcriptional regulation of CATSPER1, but previous studies have performed in silico analyses of transcription factor binding sites, including three CRE sites designated 0-2, in which CRE0 is located near the transcription start site.

OBJETIVES:

We investigate if overexpression of CREB-A and CREMτ transcription factors might regulate CATSPER1 expression.

MATERIAL AND METHODS:

In this study, the transcriptional regulation of the CATSPER1 gene by CREB-A and CREMτ transcriptions factors was determined by dual-luciferase assays in HEK293 and GC1-spg cells, and important CRE sites were mutated and analyzed for transcriptional regulation.

RESULTS:

The deletion of the CRE1 site dramatically increased the transcriptional activity of the CATSPER1 promoter in HEK293 and GC1-spg cells. In HEK293 cells, the CREB-A transcription factor positively regulated CATSPER1 gene expression, while the presence of CREB-A and CREMτ factors synergistically enhanced promoter activity in these cells. In contrast, deletion of CRE0 prevented any transcriptional activity of the CATSPER1 promoter in GC1-spg spermatogonial cells, but expression of either CREB-A or CREMτ restored such transcriptional activity.

CONCLUSIONS:

The human CATSPER1 promoter is positively regulated in vitro by CREB-A in HEK293 and GC1-spg cells. Both lines showed differential transcriptional regulation, which was defined by the factors and coactivators present in each cell line as well as the context in which the CRE sites were found in the promoter.

KEYWORDS:

CATSPER cation channel sperm; CREB-A; CREMtau; Promoter; Transcription

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