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Epigenetic regulation of the human p53 gene promoter by the CTCF transcription factor in transformed cell lines

Oncogene volume 29, pages 2217–2227 (2010)Cite this article

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Abstract

Epigenetic silencing of tumor suppressor gene promoters has become a more frequent phenomenon in cancer than previously anticipated. In this study we addressed the mechanisms involved in the protection of the p53 tumor suppressor gene against epigenetic silencing in human transformed cell lines. We characterized a binding site for the CCCTC-binding factor (CTCF) in the human p53 gene promoter that contributes to its transcriptional expression, and has the ability to maintain this regulatory element in a local open chromatin configuration. In the absence of CTCF we observe the incorporation of repressive histone marks, such as H3K9me3, H3K27me3 and H4K20me3, in different sub-domains of the upstream regulatory sequence. This evidence suggests that CTCF protects the p53 gene promoter against repressive histone marks. Notably, no apparent direct correlation between repression and DNA hypermethylation has been detected. Together, we present evidence supporting the relevant role of CTCF in the epigenetic regulation of tumor suppressor genes and cancer. We propose that CTCF is a strategic component responsible for the maintenance and segregation of epigenetic traits.

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Acknowledgements

We thank Inti Alberto de la Rosa-Velázquez, Catherine Farrell, Mayra Furlan-Magaril, Francisco Antequera, Abrahan Hernández-Hernández, Martín Escamilla-del-Arenal and Héctor Rincón-Arano for suggestions and constant scientific discussions. We are particularly indebted with the excellent technical assistance of Georgina Guerrero Avendaño, members of the Félix Recillas-Targa laboratory, Dr JA García-Saínz and the Instituto de Fisiología Celular, UNAM. We thank L Ongay, G Codiz and M Mora from the Unidad de Biología Molecular, IFC-UNAM, for DNA sequencing. This work was supported by the Dirección General de Asuntos del Personal Académico-Universidad Nacional Autónoma de México (IN209403 and IN214407), Consejo Nacional de Ciencia y Tecnología (CONACyT: 42653-Q and 58767) and Fundación Miguel Alemán, AC. E Soto-Reyes is supported by a PhD fellowship from CONACyT (181389) and Dirección General de estudios de Posgrado-Universidad Nacional Autónoma de México (DGEP). Additional support was provided by the PhD Graduate Program of Doctorado en Ciencias Biomédicas.

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  1. Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México, D.F., México

    E Soto-Reyes & F Recillas-Targa

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Correspondence to F Recillas-Targa.

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Soto-Reyes, E., Recillas-Targa, F. Epigenetic regulation of the human p53 gene promoter by the CTCF transcription factor in transformed cell lines. Oncogene 29, 2217–2227 (2010). https://doi.org/10.1038/onc.2009.509

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