Evidence map›Paper›PMID 27633323›Full record

ArticleGenome research2016

Binding of nuclear factor κB to noncanonical consensus sites reveals its multimodal role during the early inflammatory response.

Petros Kolovos, Theodore Georgomanolis, Anna Koeferle, Joshua D Larkin, Lilija Brant, Miloš Nikolicć, Eduardo G Gusmao, Anne Zirkel, Tobias A Knoch, Wilfred F van Ijcken and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in Genome research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing 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

33 citing papers in PubMed, 52 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Low Input Targeted Chromatin Capture (Low-T2C).Methods in molecular biology (Clifton, N.J.) · 2021
    Article
  20. Chromatin Conformation in Development and Disease.Frontiers in cell and developmental biology · 2021
    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

14 authors at 4 institutions in 3 countries.

Petros KolovosDepartment of Cell Biology, Erasmus Medical Centre, 3015 CN Rotterdam, The Netherlands.
Theodore GeorgomanolisCenter for Molecular Medicine, University of Cologne, 50931 Cologne, Germany.
Anna KoeferleSir William Dunn School of Pathology, University of Oxford, OX1 3RE Oxford, United Kingdom.
Joshua D LarkinSir William Dunn School of Pathology, University of Oxford, OX1 3RE Oxford, United Kingdom.
Lilija BrantCenter for Molecular Medicine, University of Cologne, 50931 Cologne, Germany.
Miloš NikolicćCenter for Molecular Medicine, University of Cologne, 50931 Cologne, Germany.
Eduardo G GusmaoIZKF Computational Biology Research Group, RWTH Aachen University Medical School, 52062 Aachen, Germany.
Anne ZirkelCenter for Molecular Medicine, University of Cologne, 50931 Cologne, Germany.
Tobias A KnochDepartment of Cell Biology, Erasmus Medical Centre, 3015 CN Rotterdam, The Netherlands.
Wilfred F van IjckenCenter for Biomics, Erasmus Medical Centre, 3015 GE Rotterdam, The Netherlands.
Peter R CookSir William Dunn School of Pathology, University of Oxford, OX1 3RE Oxford, United Kingdom.
Ivan G CostaIZKF Computational Biology Research Group, RWTH Aachen University Medical School, 52062 Aachen, Germany.
Frank G GrosveldDepartment of Cell Biology, Erasmus Medical Centre, 3015 CN Rotterdam, The Netherlands.
Argyris PapantonisCenter for Molecular Medicine, University of Cologne, 50931 Cologne, Germany.
University of Cologne · DEErasmus MC · NLUniversity of Oxford · GBRWTH Aachen University · DE

Funding

Wellcome Trust
6 · The paper itself

Abstract

Mammalian cells have developed intricate mechanisms to interpret, integrate, and respond to extracellular stimuli. For example, tumor necrosis factor (TNF) rapidly activates proinflammatory genes, but our understanding of how this occurs against the ongoing transcriptional program of the cell is far from complete. Here, we monitor the early phase of this cascade at high spatiotemporal resolution in TNF-stimulated human endothelial cells. NF-κB, the transcription factor complex driving the response, interferes with the regulatory machinery by binding active enhancers already in interaction with gene promoters. Notably, >50% of these enhancers do not encode canonical NF-κB binding motifs. Using a combination of genomics tools, we find that binding site selection plays a key role in NF-κΒ-mediated transcriptional activation and repression. We demonstrate the latter by describing the synergy between NF-κΒ and the corepressor JDP2. Finally, detailed analysis of a 2.8-Mbp locus using sub-kbp-resolution targeted chromatin conformation capture and genome editing uncovers how NF-κΒ that has just entered the nucleus exploits pre-existing chromatin looping to exert its multimodal role. This work highlights the involvement of topology in cis-regulatory element function during acute transcriptional responses, where primary DNA sequence and its higher-order structure constitute a regulatory context leading to either gene activation or repression.

Indexed as

Consensus SequencePromoter Regions, GeneticTranscriptional ActivationCells, CulturedChromatinGene EditingHumansHuman Umbilical Vein Endothelial CellsInflammationNF-kappa BProtein BindingRepressor ProteinsTumor Necrosis Factor-alphaChromatinJDP2 protein, humanNF-kappa BRepressor ProteinsTumor Necrosis Factor-alpha

Identifiers

PMID27633323
PMCPMC5088591
OpenAlexW2520029120

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.