Evidence map›Paper›PMID 39893191›Full record

ArticleNature communications2025

Effective in vivo binding energy landscape illustrates kinetic stability of RBPJ-DNA binding.

Duyen Huynh, Philipp Hoffmeister, Tobias Friedrich, Kefan Zhang, Marek Bartkuhn, Francesca Ferrante, Benedetto Daniele Giaimo, Rhett A Kovall, Tilman Borggrefe, Franz Oswald and 1 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Article
  2. Article
  3. Invariant nonequilibrium dynamics in gene regulation optimize information flow.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  4. Article
  5. Article
  6. Article
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  8. Review
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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.

Duyen Huynh *Institute of Experimental Physics and IQST, Ulm University, Ulm, Germany.
Philipp Hoffmeister *Clinic of Internal Medicine I, University Medical Center Ulm, Ulm, Germany.
Tobias FriedrichInstitute of Biochemistry, Justus-Liebig-Universität Gießen, Gießen, Germany.ORCID http://orcid.org/0000-0003-4014-8678
Kefan ZhangInstitute of Experimental Physics and IQST, Ulm University, Ulm, Germany.
Marek BartkuhnBiomedical Informatics and Systems Medicine, Justus-Liebig-Universität Gießen, Gießen, Germany.ORCID http://orcid.org/0000-0001-6872-9082
Francesca FerranteInstitute of Biochemistry, Justus-Liebig-Universität Gießen, Gießen, Germany.
Benedetto Daniele GiaimoInstitute of Biochemistry, Justus-Liebig-Universität Gießen, Gießen, Germany.ORCID http://orcid.org/0000-0003-0384-325X
Rhett A KovallDepartment of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Tilman BorggrefeInstitute of Biochemistry, Justus-Liebig-Universität Gießen, Gießen, Germany.ORCID http://orcid.org/0000-0003-4325-5452
Franz OswaldClinic of Internal Medicine I, University Medical Center Ulm, Ulm, Germany. franz.oswald@uni-ulm.de.ORCID http://orcid.org/0000-0002-2923-5765
J Christof M GebhardtInstitute of Experimental Physics and IQST, Ulm University, Ulm, Germany. christof.gebhardt@uni-ulm.de.ORCID http://orcid.org/0000-0003-1900-600X

Funding

Deutsche Forschungsgemeinschaft (German Research Foundation) 217328187)Deutsche Forschungsgemeinschaft (German Research Foundation) 316249678Deutsche Forschungsgemeinschaft (German Research Foundation) 422780363Deutsche Forschungsgemeinschaft (German Research Foundation) 427512076Deutsche Forschungsgemeinschaft (German Research Foundation) 447235146Deutsche Forschungsgemeinschaft (German Research Foundation) 450627322Deutsche Forschungsgemeinschaft (German Research Foundation) 468578170Deutsche Forschungsgemeinschaft (German Research Foundation) TRR81- A12EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020) 637987National Science Foundation (NSF) 1715822
6 · The paper itself

Abstract

Transcription factors (TFs) such as RBPJ in Notch signaling bind to specific DNA sequences to regulate transcription. How TF-DNA binding kinetics and cofactor interactions modulate gene regulation is mostly unknown. We determine the binding kinetics, transcriptional activity, and genome-wide chromatin occupation of RBPJ and mutant variants by live-cell single-molecule tracking, reporter assays, and ChIP-Seq. Importantly, the search time of RBPJ exceeds its residence time, indicating kinetic rather than thermodynamic binding stability. Impaired RBPJ-DNA binding as in Adams-Oliver-Syndrome affect both target site association and dissociation, while impaired cofactor binding mainly alters association and unspecific binding. Moreover, our data point to the possibility that cofactor binding contributes to target site specificity. Findings for other TFs comparable to RBPJ indicate that kinetic rather than thermodynamic DNA binding stability might prevail in vivo. We propose an effective in vivo binding energy landscape of TF-DNA interactions as instructive visualization of binding kinetics and mutation-induced changes.

Indexed as

DNAImmunoglobulin J Recombination Signal Sequence-Binding ProteinAnimalsBinding SitesChromatinHEK293 CellsHumansKineticsMiceMutationProtein BindingThermodynamicsChromatinDNAImmunoglobulin J Recombination Signal Sequence-Binding ProteinRBPJ protein, human

Identifiers

PMID39893191
PMCPMC11787368

What OpenQuestion holds

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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.