De novo DNA methyltransferase activity in colorectal cancer is directed towards H3K36me3 marked CpG islands.

ABSTRACT: The aberrant gain of DNA methylation at CpG islands is frequently observed in colorectal tumours and may silence the expression of tumour suppressors such as MLH1. Current models propose that these CpG islands are targeted by de novo DNA methyltransferases in a sequence-specific manner, but this has not been tested. Using ectopically integrated CpG islands, here we find that aberrantly methylated CpG islands are subject to low levels of de novo DNA methylation activity in colorectal cancer cells. By delineating DNA methyltransferase targets, we find that instead de novo DNA methylation activity is targeted primarily to CpG islands marked by the histone modification H3K36me3, a mark associated with transcriptional elongation. These H3K36me3 marked CpG islands are heavily methylated in color

SUBMITTER: Masalmeh RHA 

PROVIDER: S-EPMC7846778 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature