Evidence map›Paper›PMID 28300471›Full record

ArticleEpigenetics2017

Decoupling of DNA methylation and activity of intergenic LINE-1 promoters in colorectal cancer.

Natasha Vafadar-Isfahani, Christina Parr, Lara E McMillan, Juliane Sanner, Zhao Yeo, Stephen Saddington, Oliver Peacock, Hazel A Cruickshanks, Richard R Meehan, Jonathan N Lund and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Epigenetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.2field-weighted citation impact, top 45% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Many Different LINE-1 Retroelements Are Activated in Bladder Cancer.International journal of molecular sciences · 2020
    Article
  9. DNA methylation of intragenic CpG islands depends on their transcriptional activity during differentiation and disease.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

Natasha Vafadar-Isfahania School of Medicine, Royal Derby Hospital , University of Nottingham , Derby , UK.
Christina Parra School of Medicine, Royal Derby Hospital , University of Nottingham , Derby , UK.
Lara E McMillana School of Medicine, Royal Derby Hospital , University of Nottingham , Derby , UK.
Juliane Sannera School of Medicine, Royal Derby Hospital , University of Nottingham , Derby , UK.
Zhao Yeoa School of Medicine, Royal Derby Hospital , University of Nottingham , Derby , UK.
Stephen Saddingtona School of Medicine, Royal Derby Hospital , University of Nottingham , Derby , UK.
Oliver Peacocka School of Medicine, Royal Derby Hospital , University of Nottingham , Derby , UK.
Hazel A Cruickshanksb School of Biological Sciences , University of Edinburgh , Edinburgh , UK.
Richard R Meehanc MRC Human Genetics Unit , Institute of Genetics and Molecular Medicine, University of Edinburgh , Edinburgh , UK.
Jonathan N Lunda School of Medicine, Royal Derby Hospital , University of Nottingham , Derby , UK.
Cristina Tufarellia School of Medicine, Royal Derby Hospital , University of Nottingham , Derby , UK.ORCID 0000-0002-1053-4618
University of Nottingham · GBInstitute of Genetics and Cancer · GBUniversity of Edinburgh · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

AzacitidineColorectal NeoplasmsDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3BGene Expression Regulation, NeoplasticHCT116 CellsHumansLong Interspersed Nucleotide ElementsPromoter Regions, GeneticAzacitidineDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3BDNMT1 protein, humanchromatincolorectal cancerCRCH4K20me3L1-ASPL1PA2LCTLINE-1methylationretrotransposons

Identifiers

PMID28300471
PMCPMC5501206
OpenAlexW2595060373

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.