Mismatch Repair Proteins Initiate Epigenetic Alterations during Inflammation-Driven Tumorigenesis.

ABSTRACT: Aberrant silencing of genes by DNA methylation contributes to cancer, yet how this process is initiated remains unclear. Using a murine model of inflammation-induced tumorigenesis, we tested the hypothesis that inflammation promotes recruitment of epigenetic proteins to chromatin, initiating methylation and gene silencing in tumors. Compared with normal epithelium and noninflammation-induced tumors, inflammation-induced tumors gained DNA methylation at CpG islands, some of which are associated with putative tumor suppressor genes. Hypermethylated genes exhibited enrichment of repressive chromatin marks and reduced expression prior to tumorigenesis, at a time point coinciding with peak levels of inflammation-associated DNA damage. Loss of MutS homolog 2 (MSH2), a mismatch repair (MMR) prote

SUBMITTER: Maiuri AR 

PROVIDER: S-EPMC5516887 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature