Mapping Patterns of CpG Island Methylation in Normal and Neoplastic Cells Implicates Both Upstream and Downstream Regions inde Novo Methylation

摘要: Abstract Promoter region CpG island methylation is associated with tumor suppressor gene silencing in neoplasia. GenBank sequence analyses revealed that a number of islands are juxtaposed to multiple Alu repeats, which have been proposed as “de novo centers.” These also contain Sp1 elements located upstream and downstream transcription start, shown protect from methylation. We mapped the patterns E-cadherin(E-cad) von Hippel-Lindau (VHL) regions normal neoplastic cells. Although unmethylated tissue, these were embedded between densely methylated flanking containing repeats. flanks segregated unmethylated, sites by Sp1-rich boundary regions. Finally, human fibroblasts overexpressing DNA methyltransferase, de novomethylation E-cad initially involved sequences at both ends adjacent, progressed time encompass entire region. Together, data suggest boundaries exist maintain state tissue may be progressively overridden, eliciting thede