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

Original Article

Oncogene (2010) 29, 2217–2227; doi:10.1038/onc.2009.509; published online 25 January 2010
Epigenetic regulation of the human p53 gene promoter by the CTCF transcription factor in transformed cell lines

E Soto-Reyes1 and F Recillas-Targa1

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

Correspondence: Dr F Recillas-Targa, Instituto de Fisiología Celular, Departamento de Genética Molecular, Universidad Nacional Autónoma de México, Apartado Postal 70-242, Mexico City, D.F., 04510, México. E-mail: frecilla@ifc.unam.mx

Received 18 May 2009; Revised 3 December 2009; Accepted 13 December 2009; Published online 25 January 2010.
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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.