Evidence map›Paper›PMID 28448736›Full record

ArticleEpigenetics2017

Orphan CpG islands define a novel class of highly active enhancers.

Joshua S K Bell, Paula M Vertino

Open access · bronzeAbstract 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 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

31 citing papers in PubMed, 65 citations in OpenAlex.

  1. Review
  2. Interplay Between 3D Chromatin Architecture and Gene Regulation at theInternational journal of molecular sciences · 2025
    Article
  3. Article
  4. Prediction of Enhancer RNAs in Chicken Genome.International journal of molecular sciences · 2025
    Article
  5. Roles of transposable elements and DNA methylation in the formation of CpG islands and CpG-depleted regulatory elements.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  6. Article
  7. Article
  8. Role of the histone variant H2A.Z.1 in memory, transcription, and alternative splicing is mediated by lysine modification.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024
    Article
  9. Article
  10. Article
  11. Human mutation · 2024
    Article
  12. Transcription factor expression repertoire basis for epigenetic and transcriptional subtypes of colorectal cancers.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Intragenic CpG Islands and Their Impact on Gene Regulation.Frontiers in cell and developmental biology · 2022
    Review
  18. Article
  19. Article
  20. Review
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

2 authors at 1 institution in 1 country.

Joshua S K Bella Department of Radiation Oncology , Emory University School of Medicine , Atlanta , GA , USA.
Paula M Vertinoa Department of Radiation Oncology , Emory University School of Medicine , Atlanta , GA , USA.
Emory University · US

Funding

GENESIS AND CONSEQUENCES OF ABERRANT DNA METHYLATIONR01CA077337 · NCI · EMORY UNIVERSITY · PI VERTINO, PAULA M. · 1998 to 2016
$3.4M
DNA demethylation and the reprogramming of transcriptional dynamicsF31CA186676 · NCI · EMORY UNIVERSITY · PI BELL, JOSHUA STEVEN · 2014 to 2016
$129k
NCI NIH HHS F31 CA186676NCI NIH HHS R01 CA077337
6 · The paper itself

Abstract

CpG islands (CGI) are critical genomic regulatory elements that support transcriptional initiation and are associated with the promoters of most human genes. CGI are distinguished from the bulk genome by their high CpG density, lack of DNA methylation, and euchromatic features. While CGI are canonically known as strong promoters, thousands of 'orphan' CGI lie far from any known transcript, leaving their function an open question. We undertook a comprehensive analysis of the epigenetic state of orphan CGI across over 100 cell types. Here we show that most orphan CGI display the chromatin features of active enhancers (H3K4me1, H3K27Ac) in at least one cell type. Relative to classical enhancers, these enhancer CGI (ECGI) are stronger, as gauged by chromatin state and in functional assays, are more broadly expressed, and are more highly conserved. Likewise, ECGI engage in more genomic contacts and are enriched for transcription factor binding relative to classical enhancers. In human cancers, these epigenetic differences between ECGI vs. classical enhancers manifest in distinct alterations in DNA methylation. Thus, ECGI define a class of highly active enhancers, strengthened by the broad transcriptional activity, CpG density, hypomethylation, and chromatin features they share with promoter CGI. In addition to indicating a role for thousands of orphan CGI, these findings suggests that enhancer activity may be an intrinsic function of CGI in general and provides new insights into the evolution of enhancers and their epigenetic regulation during development and tumorigenesis.

Indexed as

Enhancer Elements, GeneticEpigenesis, GeneticCarcinogenesisChromatinCpG IslandsDNA MethylationHistonesHumansPromoter Regions, GeneticTranscription FactorsChromatinHistonesTranscription FactorsCancerchromatinDNA methylationenhancersepigeneticstranscription

Identifiers

PMID28448736
PMCPMC5501197
OpenAlexW2608482093

What OpenQuestion holds

Textmetadata
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.