Evidence map›Paper›PMID 34183853›Full record

ArticleNature genetics2021

Orphan CpG islands amplify poised enhancer regulatory activity and determine target gene responsiveness.

Tomas Pachano, Víctor Sánchez-Gaya, Thais Ealo, Maria Mariner-Faulí, Tore Bleckwehl, Helena G Asenjo, Patricia Respuela, Sara Cruz-Molina, María Muñoz-San Martín, Endika Haro and 3 more

Open access · greenAbstract read
In one paragraph

Article in Nature genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
8.3field-weighted citation impact, top 1% 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

66 citing papers in PubMed, 114 citations in OpenAlex.

  1. Review
  2. Article
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  4. Transcription and Three-Dimensional Genome Organization: Cause, Consequence, or Coordination?BioEssays : news and reviews in molecular, cellular and developmental biology · 2026
    Review
  5. Article
  6. Article
  7. Facilitators may represent a new class of regulatory elements.Current opinion in genetics & development · 2026
    Review
  8. Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. 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
  14. Individuals with intellectual disability have an increased burden ofmedRxiv : the preprint server for health sciences · 2025
    Article
  15. Review
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  20. Article

6 more citing papers are in PubMed but not listed here.

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

13 authors at 5 institutions in 3 countries.

Tomas PachanoCenter for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.ORCID http://orcid.org/0000-0003-2823-7715
Víctor Sánchez-GayaInstitute of Biomedicine and Biotechnology of Cantabria (IBBTEC), CSIC/Universidad de Cantabria/SODERCAN, Santander, Spain.
Thais EaloInstitute of Biomedicine and Biotechnology of Cantabria (IBBTEC), CSIC/Universidad de Cantabria/SODERCAN, Santander, Spain.
Maria Mariner-FaulíInstitute of Biomedicine and Biotechnology of Cantabria (IBBTEC), CSIC/Universidad de Cantabria/SODERCAN, Santander, Spain.
Tore BleckwehlCenter for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
Helena G AsenjoCentre for Genomics and Oncological Research (GENYO), Granada, Spain.ORCID http://orcid.org/0000-0003-1904-1606
Patricia RespuelaInstitute of Biomedicine and Biotechnology of Cantabria (IBBTEC), CSIC/Universidad de Cantabria/SODERCAN, Santander, Spain.
Sara Cruz-MolinaMax Planck Institute for Molecular Biomedicine, Muenster, Germany.ORCID http://orcid.org/0000-0002-9405-2244
María Muñoz-San MartínInstitute of Biomedicine and Biotechnology of Cantabria (IBBTEC), CSIC/Universidad de Cantabria/SODERCAN, Santander, Spain.ORCID http://orcid.org/0000-0002-7249-5343
Endika HaroInstitute of Biomedicine and Biotechnology of Cantabria (IBBTEC), CSIC/Universidad de Cantabria/SODERCAN, Santander, Spain.
Wilfred F J van IJckenCenter for Biomics, Erasmus University Medical Center, Rotterdam, the Netherlands.ORCID http://orcid.org/0000-0002-0421-8301
David LandeiraCentre for Genomics and Oncological Research (GENYO), Granada, Spain.
Alvaro Rada-IglesiasCenter for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany. alvaro.rada@unican.es.ORCID http://orcid.org/0000-0001-7137-1341
Universidad de Cantabria · ESUniversidad de Granada · ESUniversity of Cologne · DEErasmus MC · NLMax Planck Institute for Molecular Biomedicine · DE

Funding

European Research Council 862022
6 · The paper itself

Abstract

CpG islands (CGIs) represent a widespread feature of vertebrate genomes, being associated with ~70% of all gene promoters. CGIs control transcription initiation by conferring nearby promoters with unique chromatin properties. In addition, there are thousands of distal or orphan CGIs (oCGIs) whose functional relevance is barely known. Here we show that oCGIs are an essential component of poised enhancers that augment their long-range regulatory activity and control the responsiveness of their target genes. Using a knock-in strategy in mouse embryonic stem cells, we introduced poised enhancers with or without oCGIs within topologically associating domains harboring genes with different types of promoters. Analysis of the resulting cell lines revealed that oCGIs act as tethering elements that promote the physical and functional communication between poised enhancers and distally located genes, particularly those with large CGI clusters in their promoters. Therefore, by acting as genetic determinants of gene-enhancer compatibility, CGIs can contribute to gene expression control under both physiological and potentially pathological conditions.

Indexed as

CpG IslandsDNA MethylationEnhancer Elements, GeneticEpigenesis, GeneticGene Expression RegulationAnimalsChromatinEmbryonic Stem CellsGene Knock-In TechniquesMicePromoter Regions, GeneticChromatin

Identifiers

PMID34183853
PMCPMC7611182
OpenAlexW3176042246

What OpenQuestion holds

Textmetadata
LicenceTDM
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.