ArticleBMC cancer2011
Gain of DNA methylation is enhanced in the absence of CTCF at the human retinoblastoma gene promoter.
Article in BMC cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 30 citations in OpenAlex.
- CTCF delimits a DNA methylation transition at the intergenic region between the embryonic and adult α-globin genes.Epigenetics · 2026Article
- Beckwith-Wiedemann syndrome and large offspring syndrome involve alterations in methylome, transcriptome, and chromatin configuration.NAR molecular medicine · 2025Article
- New perspectives on DNA methylation modifications in ocular diseases.International journal of ophthalmology · 2025Review
- Methylation of Subtelomeric Chromatin Modifies the Expression of the lncRNA TERRA, Disturbing Telomere Homeostasis.International journal of molecular sciences · 2022Article
- Genomic Space ofInternational journal of molecular sciences · 2021Article
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- An IntronicFrontiers in genetics · 2020Article
- [Bioinformatics Analysis of DNA Methylation in the Promoters of LincRNA in Lung Adenocarcinoma].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2018Article
- A Tox21 Approach to Altered Epigenetic Landscapes: Assessing Epigenetic Toxicity Pathways Leading to Altered Gene Expression and Oncogenic Transformation In Vitro.International journal of molecular sciences · 2017Review
- A covalently bound inhibitor triggers EZH2 degradation through CHIP-mediated ubiquitination.The EMBO journal · 2017Article
- Article
- Article
- "Monoallelic germline methylation and sequence variant in the promoter of the RB1 gene: a possible constitutive epimutation in hereditary retinoblastoma".Clinical epigenetics · 2016Article
- A promising hypothesis of c-KIT methylation/ expression paradox in c-KIT (+) squamous cell carcinoma of uterine cervix ----- CTCF transcriptional repressor regulates c-KIT proto-oncogene expression.Diagnostic pathology · 2015Review
- Epigenetic silencing of the XAF1 gene is mediated by the loss of CTCF binding.Scientific reports · 2015Article
- The apoptosis associated tyrosine kinase gene is frequently hypermethylated in human cancer and is regulated by epigenetic mechanisms.Genes & cancer · 2014Article
- Widespread plasticity in CTCF occupancy linked to DNA methylation.Genome research · 2012Article
- Is there an epigenetic component underlying the resistance of triple-negative breast cancers to parp inhibitors?Frontiers in pharmacology · 2012Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLong-term gene silencing throughout cell division is generally achieved by DNA methylation and other epigenetic processes. Aberrant DNA methylation is now widely recognized to be associated with cancer and other human diseases. Here we addressed the contribution of the multifunctional nuclear factor CTCF to the epigenetic regulation of the human retinoblastoma (Rb) gene promoter in different tumoral cell lines.
methodsTo assess the DNA methylation status of the Rb promoter, genomic DNA from stably transfected human erythroleukemic K562 cells expressing a GFP reporter transgene was transformed with sodium bisulfite, and then PCR-amplified with modified primers and sequenced. Single- and multi-copy integrants with the CTCF binding site mutated were isolated and characterized by Southern blotting. Silenced transgenes were reactivated using 5-aza-2'-deoxycytidine and Trichostatin-A, and their expression was monitored by fluorescent cytometry. Rb gene expression and protein abundance were assessed by RT-PCR and Western blotting in three different glioma cell lines, and DNA methylation of the promoter region was determined by sodium bisulfite sequencing, together with CTCF dissociation and methyl-CpG-binding protein incorporation by chromatin immunoprecipitation assays.
resultsWe found that the inability of CTCF to bind to the Rb promoter causes a dramatic loss of gene expression and a progressive gain of DNA methylation.
conclusionsThis study indicates that CTCF plays an important role in maintaining the Rb promoter in an optimal chromatin configuration. The absence of CTCF induces a rapid epigenetic silencing through a progressive gain of DNA methylation. Consequently, CTCF can now be seen as one of the epigenetic components that allows the proper configuration of tumor suppressor gene promoters. Its aberrant dissociation can then predispose key genes in cancer cells to acquire DNA methylation and epigenetic silencing.
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