Evidence map›Paper›PMID 35075236›Full record

ArticleCommunications biology2022

Flanking sequences influence the activity of TET1 and TET2 methylcytosine dioxygenases and affect genomic 5hmC patterns.

Sabrina Adam, Julia Bräcker, Viviane Klingel, Bernd Osteresch, Nicole E Radde, Jens Brockmeyer, Pavel Bashtrykov, Albert Jeltsch

Open access · goldAbstract read
In one paragraph

Article in Communications biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

17 citing papers in PubMed, 31 citations in OpenAlex.

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  17. Pathways of DNA Demethylation.Advances in experimental medicine and biology · 2022
    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

8 authors at 1 institution in 1 country.

Sabrina AdamInstitute of Biochemistry and Technical Biochemistry, Department of Biochemistry, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.
Julia BräckerInstitute of Biochemistry and Technical Biochemistry, Department of Food Chemistry, University of Stuttgart, Allmandring 5b, 70569, Stuttgart, Germany.ORCID http://orcid.org/0000-0002-4676-6410
Viviane KlingelInstitute for Systems Theory and Automatic Control, University of Stuttgart, Pfaffenwaldring 9, 70569, Stuttgart, Germany.
Bernd OstereschInstitute of Biochemistry and Technical Biochemistry, Department of Food Chemistry, University of Stuttgart, Allmandring 5b, 70569, Stuttgart, Germany.
Nicole E RaddeInstitute for Systems Theory and Automatic Control, University of Stuttgart, Pfaffenwaldring 9, 70569, Stuttgart, Germany.
Jens BrockmeyerInstitute of Biochemistry and Technical Biochemistry, Department of Food Chemistry, University of Stuttgart, Allmandring 5b, 70569, Stuttgart, Germany.
Pavel BashtrykovInstitute of Biochemistry and Technical Biochemistry, Department of Biochemistry, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.
Albert JeltschInstitute of Biochemistry and Technical Biochemistry, Department of Biochemistry, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany. albert.jeltsch@ibtb.uni-stuttgart.de.ORCID http://orcid.org/0000-0001-6113-9290
University of Stuttgart · DE

Funding

Deutsche Forschungsgemeinschaft (German Research Foundation) EXC 2075 390740016Deutsche Forschungsgemeinschaft (German Research Foundation) JE252/36Deutsche Forschungsgemeinschaft (German Research Foundation) RA1840/2-1
6 · The paper itself

Abstract

TET dioxygenases convert 5-methylcytosine (5mC) preferentially in a CpG context into 5-hydroxymethylcytosine (5hmC) and higher oxidized forms, thereby initiating DNA demethylation, but details regarding the effects of the DNA sequences flanking the target 5mC site on TET activity are unknown. We investigated oxidation of libraries of DNA substrates containing one 5mC or 5hmC residue in randomized sequence context using single molecule readout of oxidation activity and sequence and show pronounced 20 and 70-fold flanking sequence effects on the catalytic activities of TET1 and TET2, respectively. Flanking sequence preferences were similar for TET1 and TET2 and also for 5mC and 5hmC substrates. Enhanced flanking sequence preferences were observed at non-CpG sites together with profound effects of flanking sequences on the specificity of TET2. TET flanking sequence preferences are reflected in genome-wide and local patterns of 5hmC and DNA demethylation in human and mouse cells indicating that they influence genomic DNA modification patterns in combination with locus specific targeting of TET enzymes.

Indexed as

5-MethylcytosineAnimalsBase SequenceChromatography, High Pressure LiquidCloning, MolecularComputational BiologyDioxygenasesDNA-Binding ProteinsGene Expression RegulationGenomicsMiceProto-Oncogene ProteinsTandem Mass Spectrometry5-hydroxymethylcytosine5-MethylcytosineDioxygenasesDNA-Binding ProteinsProto-Oncogene ProteinsTET1 protein, mouseTet2 protein, mouse

Identifiers

PMID35075236
PMCPMC8786823
OpenAlexW4207022292

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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.