Abnormal methylation in the NDUFA13 gene promoter of breast cancer cells breaks the cooperative DNA recognition by transcription factors.

ABSTRACT: Selective DNA binding by transcription factors (TFs) is crucial for the correct regulation of DNA transcription. In healthy cells, promoters of active genes are hypomethylated. A single CpG methylation within a TF response element (RE) may change the binding preferences of the protein, thus causing the dysregulation of transcription programs. Here, we investigate a molecular mechanism driving the downregulation of the NDUFA13 gene, due to hypermethylation, which is associated with multiple cancers. Using bioinformatic analyses of breast cancer cell line MCF7, we identify a hypermethylated region containing the binding sites of two TFs dimers, CEBPB and E2F1-DP1, located 130 b.p. from the gene transcription start site. All-atom extended MD simulations of wild type and methylated DNA

SUBMITTER: Horberg J 

PROVIDER: S-EPMC10392677 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature