CTCF is a DNA methylation-sensitive positive regulator of the INK/ARF locus - PubMed (original) (raw)
. 2010 Feb 5;392(2):129-34.
doi: 10.1016/j.bbrc.2009.12.159. Epub 2010 Jan 4.
Affiliations
- PMID: 20051228
- DOI: 10.1016/j.bbrc.2009.12.159
CTCF is a DNA methylation-sensitive positive regulator of the INK/ARF locus
Carmen Rodriguez et al. Biochem Biophys Res Commun. 2010.
Abstract
The INK4B-ARF-INK4A (INK/ARF) locus is composed of three tumor suppressor genes, which are kept silenced by DNA methylation in different cancer types. In addition, a non-coding RNA (ANRIL) is transcribed in the anti-sense orientation upstream of the ARF gene. The resulting divergent promoter region is bound by the chromatin insulator protein CTCF in association with histone H3 tri-methylated on lysine 4, irrespective of transcription of ANRIL and ARF. Methylation of the overlapping CpG island abolishes CTCF binding and the associated modification, which can be restored by 5-Aza-2'-deoxycytidine (5-Aza-dC) treatment. shRNA knock down of CTCF expression dramatically reduces the induction of ANRIL and ARF, but also that of INK4A and INK4B expression by 5-Aza-dC. We propose that CTCF is an essential factor for transcription of the INK/ARF locus and that abrogation of its binding by DNA methylation contributes to the permanent silencing of several genes of the locus in tumors.
2010 Elsevier Inc. All rights reserved.
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