Masalmeh, Roza H. Ali and Taglini, Francesca and Rubio-Ramon, Cristina and Musialik, Kamila I. and Higham, Jonathan and Davidson-Smith, Hazel and Kafetzopoulos, Ioannis and Pawlicka, Kamila P. and Finan, Hannah M. and Clark, Richard and Wills, Jimi and Finch, Andrew J. and Murphy, Lee and Sproul, Duncan (2021) De novo DNA methyltransferase activity in colorectal cancer is directed towards H3K36me3 marked CpG islands. Nature Communications, 12 (1): 694. ISSN 2041-1723
Full text not available from this repository.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 colorectal tumours and the normal colon suggesting that de novo DNA methyltransferase activity at CpG islands in colorectal cancer is focused on similar targets to normal tissues and not greatly remodelled by tumourigenesis.