Methylation of CpG island transcription factor binding sites is unnecessary for aberrant silencing of the human MGMT gene.

摘要: Aberrant transcriptional inactivation of the non-X-linked human O-6-methylguanine DNA methyltransferase (MGMT) gene has been associated with loss open chromatin structure and increases in cytosine methylation Sp1-binding region 5′-CpG island gene. To examine necessity these events for silencing, we have isolated characterized a subline MGMT+ T98G glioma cells. The subline, T98Gs, does not express MGMT activity or mRNA, exhibits no vivo DNA-protein interactions at Sp1-like binding sites island. While CpG is less accessible to exogenously added restriction enzymes T98Gs nuclei than nuclei, it similarly methylated both cell lines 5′ 3′ transcription factor sites, unmethylated encompassing sites. Inappropriate MGMT, therefore, require within Rather, silencing exclusion from most closely condensed structure, which turn indirectly influenced by distant methylation.