The role of DNA methylation in expression of the p19/p16 locus in human bladder cancer cell lines

摘要: Methylation of CpG sites in the control regions tumor suppressor genes may be an important mechanism for their heritable, yet reversible, transcriptional inactivation. These changes methylation impair proper expression and/or function cell cycle regulatory and confer a selective growth advantage to affected cells. Detailed analysis using genomic bisulfite sequencing was performed on series subclones bladder cancer line which hypermethylated p16 gene had been reactivated by transient treatment with 5-aza-2'-deoxycytidine. island promoter human cells did not stop formation transcript initiated 20 kb upstream p19 but prevent transcript. Furthermore, we show that reactivant clones expressed at varying levels contained heterogeneous patterns, suggesting can occur even presence relatively heavily methylated coding region. We also present first functional evidence only small number significantly down-regulate activity, thus providing support model progressive inactivation this DNA methylation.