Silencing of p16/CDKN2 Expression in Human Gliomas by Methylation and Chromatin Condensation

摘要: The product of the p16/CDKN2 locus, p16ink4, negatively regulates cell cycle through binding and inactivation cyclin-dependent kinases (CDKs) 4 6. This locus is frequently targeted for deletion in lines primary tumor tissues. In gliomas, although up to 50% do not have detectable expression protein or mRNA, often gene wild type sequence. Here, we tested hypothesis that transcriptional repression gliomas may be mediated by aberrant methylation CpG island, which 5' region locus. Partial rather than complete was detected 24% (10 42) regardless grade, but observed normal brain (0 10). We whether this partial could inhibit a human line suppressed associated with both tightly compacted chromatin around promoter. Exposure these cells 5-aza-2-deoxycytidine resulted dramatic increase promoter accessibility induction expression, indicating structure, island methylation, are intimately associated. Taken together, data suggest occurs only subset within methylation-associated many common cancers mechanistically result from structural changes containing