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

Autor:	Masalmeh RHA; MRC Human Genetics Unit, IGMM, University of Edinburgh, Edinburgh, UK., Taglini F; MRC Human Genetics Unit, IGMM, University of Edinburgh, Edinburgh, UK.; CRUK Edinburgh Centre, IGMM, University of Edinburgh, Edinburgh, UK., Rubio-Ramon C; MRC Human Genetics Unit, IGMM, University of Edinburgh, Edinburgh, UK.; CRUK Edinburgh Centre, IGMM, University of Edinburgh, Edinburgh, UK., Musialik KI; MRC Human Genetics Unit, IGMM, University of Edinburgh, Edinburgh, UK.; CRUK Edinburgh Centre, IGMM, University of Edinburgh, Edinburgh, UK., Higham J; MRC Human Genetics Unit, IGMM, University of Edinburgh, Edinburgh, UK., Davidson-Smith H; MRC Human Genetics Unit, IGMM, University of Edinburgh, Edinburgh, UK., Kafetzopoulos I; MRC Human Genetics Unit, IGMM, University of Edinburgh, Edinburgh, UK.; CRUK Edinburgh Centre, IGMM, University of Edinburgh, Edinburgh, UK., Pawlicka KP; MRC Human Genetics Unit, IGMM, University of Edinburgh, Edinburgh, UK.; CRUK Edinburgh Centre, IGMM, University of Edinburgh, Edinburgh, UK., Finan HM; MRC Human Genetics Unit, IGMM, University of Edinburgh, Edinburgh, UK.; CRUK Edinburgh Centre, IGMM, University of Edinburgh, Edinburgh, UK., Clark R; Edinburgh Clinical Research Facility, University of Edinburgh, Edinburgh, UK., Wills J; CRUK Edinburgh Centre, IGMM, University of Edinburgh, Edinburgh, UK., Finch AJ; CRUK Edinburgh Centre, IGMM, University of Edinburgh, Edinburgh, UK.; Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of London, London, UK., Murphy L; Edinburgh Clinical Research Facility, University of Edinburgh, Edinburgh, UK., Sproul D; MRC Human Genetics Unit, IGMM, University of Edinburgh, Edinburgh, UK. Duncan.Sproul@igmm.ed.ac.uk.; CRUK Edinburgh Centre, IGMM, University of Edinburgh, Edinburgh, UK. Duncan.Sproul@igmm.ed.ac.uk.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2021 Jan 29; Vol. 12 (1), pp. 694. Date of Electronic Publication: 2021 Jan 29.
DOI:	10.1038/s41467-020-20716-w
Abstrakt:	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.
Databáze:	MEDLINE
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