Methylation in hMLH1 promoter interferes with its binding to transcription factor CBF and inhibits gene expression

The Regulatory Mechanism of the LY6K Gene Expression in Human Breast Cancer Cells

“…Second, gene silencing is caused by inhibiting the binding of sequencespecific transcription factors to their binding sites containing CpG (35). Third, CpG site modifications affect transcription factor binding affinity but are not part of the binding site (36). We also demonstrated that methylation at a CpG site closely located to the AP-1 binding site may reduce the risk of breast cancer by effectively interfering with AP-1 binding (Fig.…”

MLH1 Polymorphisms and Cancer risk: a Meta-analysis Based on 33 Case-control Studies

“…Some study has indicated that the SNP -93G>A may increase the susceptibility of the promoter sequence to methylation. Because this polymorphism is located in a CpG island (which occurs at the cytosines of the CpG dinucleotides, and often occurs in clusters), adjacent to CpG cites that are able to undergo methylation (Deng et al, 2001). Goodfellow et al (2003) reported >20% MLH1 gene promoter methylation occurred in a large series of endometrial carcinomas.…”

Germline, somatic and epigenetic events underlying mismatch repair deficiency in colorectal and HNPCC-related cancers

“…Deng et al (1999) examined different regions of the hMLH1 promoter, and found that methylation of CpG sites in region 2 correlated best with MSI and hMLH1 protein loss in colorectal cancer cell lines. Moreover, this group has shown by functional assay that this proximal region of the hMLH1 promoter is capable of driving transcription, and methylation of this region is more important than the upstream regions in inhibiting transcription (Deng et al, 2001). Subsequently, others have demonstrated methylation in the upstream regions both in normal mucosa and a small number of colorectal cancers without protein loss or MSI phenotype (Deng et al, 2002).…”