Evidence map›Paper›PMID 25259795›Full record

ArticleeLife2014

High-throughput engineering of a mammalian genome reveals building principles of methylation states at CG rich regions.

Arnaud R Krebs, Sophie Dessus-Babus, Lukas Burger, Dirk Schübeler

Abstract read
In one paragraph

Article in eLife, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
–field-weighted citation impact
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

55 citing papers in PubMed.

  1. Synthetic Regulatory Genomics.Annual review of genomics and human genetics · 2026
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  16. Intragenic CpG Islands and Their Impact on Gene Regulation.Frontiers in cell and developmental biology · 2022
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors.

Arnaud R KrebsFriedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Sophie Dessus-BabusFriedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Lukas BurgerFriedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Dirk SchübelerFriedrich Miescher Institute for Biomedical Research, Basel, Switzerland.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The majority of mammalian promoters are CpG islands; regions of high CG density that require protection from DNA methylation to be functional. Importantly, how sequence architecture mediates this unmethylated state remains unclear. To address this question in a comprehensive manner, we developed a method to interrogate methylation states of hundreds of sequence variants inserted at the same genomic site in mouse embryonic stem cells. Using this assay, we were able to quantify the contribution of various sequence motifs towards the resulting DNA methylation state. Modeling of this comprehensive dataset revealed that CG density alone is a minor determinant of their unmethylated state. Instead, these data argue for a principal role for transcription factor binding sites, a prediction confirmed by testing synthetic mutant libraries. Taken together, these findings establish the hierarchy between the two cis-encoded mechanisms that define the DNA methylation state and thus the transcriptional competence of CpG islands.

Indexed as

High-Throughput Nucleotide SequencingAnimalsBase SequenceCell DifferentiationCpG IslandsDNA MethylationEmbryonic Stem CellsGene LibraryGenetic EngineeringGenomeHumansMammalsMiceModels, GeneticProtein BindingRecombinasesRecombinasesTranscription FactorschromosomesDNA methylationepigeneticsevolutionary biologygene regulationgenesgenomicshigh throughput genome editinghumanmouse

Identifiers

PMID25259795
PMCPMC4381937

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Registered trials

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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.