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| Methyl-CpG binding proteins identify novel sites of epigenetic inactivation in human cancer |
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| Author(s): Ballestar E, Paz MF, Valle L, Wei S, Fraga MF, Espada J, Cigudosa JC, Huang THM, Esteller M |
| Source: EMBO JOURNAL Volume: 22 Issue: 23 Pages: 6335-6345 Published: DEC 1 2003 |
| Times Cited: 125 References: 44 |
| Abstract: Methyl-CpG binding proteins (MBDs) mediate histone deacetylase-dependent transcriptional silencing at methylated CpG islands. Using chromatin immunoprecitation (ChIP) we have found that gene-specific profiles of MBDs exist for hypermethylated promoters of breast cancer cells, whilst a common pattern of histone modifications is shared. This unique distribution of MBDs is also characterized in chromosomes by comparative genomic hybridization of immunoprecipitated DNA and immunolocalization. Most importantly, we demonstrate that MBD association to methylated DNA serves to identify novel targets of epigenetic inactivation in human cancer. We combined the ChIP assay of MBDs with a CpG island microarray (ChIP on chip). The scenario revealed shows that, while many genes are regulated by multiple MBDs, others are associated with a single MBD. These target genes displayed methylation- associated transcriptional silencing in breast cancer cells and primary tumours. The candidates include the homeobox gene PAX6, the prolactin hormone receptor, and dipeptidylpeptidase IV among others. Our results support an essential role for MBDs in gene silencing and, when combined with genomic strategies, their potential to 'catch' new hypermethylated genes in cancer. |
| Document Type: Article |
| Language: English |
| Reprint Address: Esteller, M (reprint author), Spanish Natl Canc Ctr, Mol Pathol Programme, Epigenet Lab, Melchor Fernandez Almagro 3, Madrid 28029, Spain |
Addresses:
1. Spanish Natl Canc Ctr, Mol Pathol Programme, Epigenet Lab, Madrid 28029, Spain
2. Spanish Natl Canc Ctr, Biotechnol Programme, Cytogenet Unit, Madrid, Spain
3. Univ Missouri, Sch Med, Ellis Fischel Canc Ctr, Dept Pathol & Anat Sci, Columbia, MO 65203 USA |
| Publisher: OXFORD UNIV PRESS, GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: 753FP |
| ISSN: 0261-4189 |
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