Final published version
Licence: CC BY: Creative Commons Attribution 4.0 International License
Research output: Working paper › Preprint
Research output: Working paper › Preprint
}
TY - UNPB
T1 - De novo DNA methyltransferase activity in colorectal cancer is directed towards H3K36me3 marked CpG islands
AU - Ali Masalmeh, R.H.
AU - Rubio-Ramon, C.
AU - Taglini, F.
AU - Higham, J.
AU - Davidson-Smith, H.
AU - Clark, R.
AU - Wills, J.
AU - Finch, A.J.
AU - Murphy, L.
AU - Sproul, D.
PY - 2019/6/21
Y1 - 2019/6/21
N2 - The aberrant gain of DNA methylation at CpG islands (CGIs) is frequently observed in colorectal tumours and may silence the expression of tumour suppressors such as MLH1. Current models propose that these CGIs are targeted by de novo DNA methyltransferases (DNMTs) in a sequence-specific manner but this has not been tested. Using ectopically integrated CGIs, we find that aberrantly methylated CGIs are subject to low levels of de novo DNMT activity in colorectal cancer cells. By delineating DNMT targets, we find that instead de novo DNMT activity is targeted primarily to CGIs marked by the histone modification H3K36me3, a mark associated with transcriptional elongation. These H3K36me3 marked CGIs are heavily methylated in colorectal tumours and the normal colon suggesting that de novo DNMT activity at CGIs in colorectal cancer is focused on similar targets to normal tissues and not greatly remodelled by tumourigenesis.
AB - The aberrant gain of DNA methylation at CpG islands (CGIs) is frequently observed in colorectal tumours and may silence the expression of tumour suppressors such as MLH1. Current models propose that these CGIs are targeted by de novo DNA methyltransferases (DNMTs) in a sequence-specific manner but this has not been tested. Using ectopically integrated CGIs, we find that aberrantly methylated CGIs are subject to low levels of de novo DNMT activity in colorectal cancer cells. By delineating DNMT targets, we find that instead de novo DNMT activity is targeted primarily to CGIs marked by the histone modification H3K36me3, a mark associated with transcriptional elongation. These H3K36me3 marked CGIs are heavily methylated in colorectal tumours and the normal colon suggesting that de novo DNMT activity at CGIs in colorectal cancer is focused on similar targets to normal tissues and not greatly remodelled by tumourigenesis.
U2 - 10.1101/676346
DO - 10.1101/676346
M3 - Preprint
BT - De novo DNA methyltransferase activity in colorectal cancer is directed towards H3K36me3 marked CpG islands
PB - bioRxiv
ER -