The polyaromatic hydrocarbon β-naphthoflavone alters binding of YY1, Sp1, and Sp3 transcription factors to the Dp71 promoter in hepatic cells

Becerril‑Esquivel,Carolina; Peñuelas‑Urquides,Katia; Blancas‑Sánchez,Erik; Zapata‑Benavides,Pablo; Silva‑Ramírez,Beatriz; Chávez‑Reyes,Arturo; Castorena‑Torres,Fabiola; Cisneros,Bulmaro; Bermúdez de León,Mario

doi:10.3892/mmr.2018.8626

The polyaromatic hydrocarbon β-naphthoflavone alters binding of YY1, Sp1, and Sp3 transcription factors to the Dp71 promoter in hepatic cells

Authors:
- Carolina Becerril‑Esquivel
- Katia Peñuelas‑Urquides
- Erik Blancas‑Sánchez
- Pablo Zapata‑Benavides
- Beatriz Silva‑Ramírez
- Arturo Chávez‑Reyes
- Fabiola Castorena‑Torres
- Bulmaro Cisneros
- Mario Bermúdez de León
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Affiliations: Departamento de Biología Molecular, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Monterrey, Nuevo León 64720, México, Universidad Autónoma de Nuevo León, UANL, Facultad de Ciencias Biológicas, San Nicolás de los Garza, Nuevo León 66451, México, Departamento de Inmunogenética, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Monterrey, Nuevo León 64720, México, Centro de Investigación y de Estudios Avanzados del IPN Unidad Monterrey, Apodaca, Nuevo León 66600, México, Escuela de Medicina, Tecnológico de Monterrey, Monterrey, Nuevo León 64710, México, Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del IPN unidad Zacatenco, Ciudad de México 07360, México
Published online on: February 21, 2018 https://doi.org/10.3892/mmr.2018.8626
Pages: 6150-6155

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Abstract

The smallest product of the Duchenne muscular dystrophy gene, dystrophin (Dp)71, is ubiquitously expressed in nonmuscle tissues. We previously showed that Dp71 expression in hepatic cells is modulated in part by stimulating factor 1 (Sp1), stimulating protein 3 (Sp3), and yin yang 1 (YY1) transcription factors, and that the polyaromatic hydrocarbon, β-naphthoflavone (β‑NF), downregulates Dp71 expression. The aim of the present study was to determine whether β‑NF represses Dp71 expression by altering mRNA stability or its promoter activity. Reverse transcription‑quantitative polymerase chain reaction was used to measure half‑life mRNA levels in β‑NF‑treated cells exposed to actinomycin D, an inhibitor of transcription, for 0, 4, 8, 12 and 16 h. Transient transfections with a plasmid carrying the Dp71 basal promoter fused to luciferase reporter gene were carried out in control and β‑NF‑treated cells. Electrophoretic mobility shift assays (EMSAs) were performed with labeled probes, corresponding to Dp71 promoter sequences, and nuclear extracts of control and β‑NF‑treated cells. To the best of our knowledge, the results demonstrated for the first time that this negative regulation takes place at the promoter level rather than the mRNA stability level. Interestingly, using EMSAs, β‑NF reduced binding of YY1, Sp1, and Sp3 to the Dp71 promoter. It also suggests that β‑NF may modulate the expression of other genes regulated by these transcription factors. In conclusion, β‑NF represses Dp71 expression in hepatic cells by altering binding of YY1, Sp1, and Sp3 to the Dp71 promoter.

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