A Profile of Methyl-CpG Binding Domain Protein Occupancy of Hypermethylated Promoter CpG Islands of Tumor Suppressor Genes in Human Cancer
Open Access
- 1 September 2006
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 66 (17), 8342-8346
- https://doi.org/10.1158/0008-5472.can-06-1932
Abstract
Methyl-CpG binding domain (MBD) proteins have been shown to couple DNA methylation to transcriptional repression. This biological property suggests a role for MBD proteins in the silencing of tumor suppressor genes that are hypermethylated at their promoter CpG islands in cancer cells. Despite the demonstration of the presence of MBDs in the methylated promoter of several genes, we still ignore how general and specific is this association. Here, we investigate the profile of MBD occupancy in a large panel of tumor suppressor gene promoters and cancer cell lines. Our study shows that most hypermethylated promoters are occupied by MBD proteins, whereas unmethylated promoters are generally devoid of MBDs, with the exception of MBD1. Treatment of cancer cells with the demethylating agent 5-aza-2′-deoxycytidine results in CpG island hypomethylation, MBD release, and gene reexpression, reinforcing the notion that association of MBDs with methylated promoters is methylation-dependent. Whereas several promoters are highly specific in recruiting a particular set of MBDs, other promoters seem to be less exclusive. Our results indicate that MBDs have a great affinity in vivo for binding hypermethylated promoter CpG islands of tumor suppressor genes, with a specific profile of MBD occupancy that it is gene and tumor type specific. (Cancer Res 2006; 66(17): 8342-6)Keywords
Other Versions
This publication has 24 references indexed in Scilit:
- A Family of Human Zinc Finger Proteins That Bind Methylated DNA and Repress TranscriptionMolecular and Cellular Biology, 2006
- The Thymine DNA Glycosylase MBD4 Represses Transcription and Is Associated with Methylated p16INK4a and hMLH1 GenesMolecular and Cellular Biology, 2005
- Transcriptional Gene Silencing Promotes DNA Hypermethylation through a Sequential Change in Chromatin Modifications in Cancer CellsCancer Research, 2004
- CpG island hypermethylation and tumor suppressor genes: a booming present, a brighter futureOncogene, 2002
- Methyl-CpG Binding Domain Protein 2 Represses Transcription from Hypermethylated π-Class Glutathione S-Transferase Gene Promoters in Hepatocellular Carcinoma CellsPublished by Elsevier BV ,2002
- The p120 catenin partner Kaiso is a DNA methylation-dependent transcriptional repressorGenes & Development, 2001
- Methylation mattersJournal of Medical Genetics, 2001
- Closely related proteins MBD2 and MBD3 play distinctive but interacting roles in mouse developmentGenes & Development, 2001
- Aberrant CpG-island methylation has non-random and tumour-type–specific patternsNature Genetics, 2000
- Purification, sequence, and cellular localization of a novel chromosomal protein that binds to Methylated DNACell, 1992