Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/44695
Title: Decoupling of DNA methylation and activity of intergenic LINE-1 promoters in colorectal cancer.
Authors: Vafadar-Isfahani, N
Parr, C
McMillan, LE
Sanner, J
Yeo, Z
Saddington, S
Peacock, O
Cruickshanks, HA
Meehan, RR
Lund, JN
Tufarelli, C
First Published: 16-Mar-2017
Publisher: Taylor & Francis for Epigenetics Society
Citation: Epigenetics, 2017, 12 (6), pp. 465-475
Abstract: Hypomethylation of LINE-1 repeats in cancer has been proposed as the main mechanism behind their activation; this assumption, however, was based on findings from early studies that were biased toward young and transpositionally active elements. Here, we investigate the relationship between methylation of 2 intergenic, transpositionally inactive LINE-1 elements and expression of the LINE-1 chimeric transcript (LCT) 13 and LCT14 driven by their antisense promoters (L1-ASP). Our data from DNA modification, expression, and 5'RACE analyses suggest that colorectal cancer methylation in the regions analyzed is not always associated with LCT repression. Consistent with this, in HCT116 colorectal cancer cells lacking DNA methyltransferases DNMT1 or DNMT3B, LCT13 expression decreases, while cells lacking both DNMTs or treated with the DNMT inhibitor 5-azacytidine (5-aza) show no change in LCT13 expression. Interestingly, levels of the H4K20me3 histone modification are inversely associated with LCT13 and LCT14 expression. Moreover, at these LINE-1s, H4K20me3 levels rather than DNA methylation seem to be good predictor of their sensitivity to 5-aza treatment. Therefore, by studying individual LINE-1 promoters we have shown that in some cases these promoters can be active without losing methylation; in addition, we provide evidence that other factors (e.g., H4K20me3 levels) play prominent roles in their regulation.
DOI Link: 10.1080/15592294.2017.1300729
eISSN: 1559-2308
Links: https://www.tandfonline.com/doi/full/10.1080/15592294.2017.1300729
http://hdl.handle.net/2381/44695
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2017. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Cancer Studies and Molecular Medicine

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