Evidence map›Paper›PMID 24632838›Full record

ArticlePloS one2014

Quantitation of glucocorticoid receptor DNA-binding dynamics by single-molecule microscopy and FRAP.

Femke L Groeneweg, Martin E van Royen, Susanne Fenz, Veer I P Keizer, Bart Geverts, Jurrien Prins, E Ron de Kloet, Adriaan B Houtsmuller, Thomas S Schmidt, Marcel J M Schaaf

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
10.8field-weighted citation impact, top 2% 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

39 citing papers in PubMed, 67 citations in OpenAlex.

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  6. The mineralocorticoid receptor forms higher order oligomers upon DNA binding.Protein science : a publication of the Protein Society · 2024
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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

10 authors at 5 institutions in 2 countries.

Femke L GroenewegDepartment of Medical Pharmacology, Leiden University/LUMC, Leiden, The Netherlands.
Martin E van RoyenDepartment of Pathology, Erasmus MC, Rotterdam, The Netherlands.
Susanne FenzPhysics of Life Processes, Institute of Physics (LION), Leiden University, Leiden, The Netherlands; Cell & Developmental Biology, Biocenter, Würzburg University, Würzburg, Germany.
Veer I P KeizerMolecular Cell Biology, Institute of Biology, Leiden University, Leiden, The Netherlands.
Bart GevertsDepartment of Pathology, Erasmus MC, Rotterdam, The Netherlands.
Jurrien PrinsDepartment of Medical Pharmacology, Leiden University/LUMC, Leiden, The Netherlands; Molecular Cell Biology, Institute of Biology, Leiden University, Leiden, The Netherlands.
E Ron de KloetDepartment of Medical Pharmacology, Leiden University/LUMC, Leiden, The Netherlands.
Adriaan B HoutsmullerDepartment of Pathology, Erasmus MC, Rotterdam, The Netherlands.
Thomas S SchmidtPhysics of Life Processes, Institute of Physics (LION), Leiden University, Leiden, The Netherlands.
Marcel J M SchaafMolecular Cell Biology, Institute of Biology, Leiden University, Leiden, The Netherlands.
Leiden University · NLLeiden University Medical Center · NLErasmus MC · NLErasmus University Rotterdam · NLUniversity of Würzburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Recent advances in live cell imaging have provided a wealth of data on the dynamics of transcription factors. However, a consistent quantitative description of these dynamics, explaining how transcription factors find their target sequences in the vast amount of DNA inside the nucleus, is still lacking. In the present study, we have combined two quantitative imaging methods, single-molecule microscopy and fluorescence recovery after photobleaching, to determine the mobility pattern of the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR), two ligand-activated transcription factors. For dexamethasone-activated GR, both techniques showed that approximately half of the population is freely diffusing, while the remaining population is bound to DNA. Of this DNA-bound population about half the GRs appeared to be bound for short periods of time (∼ 0.7 s) and the other half for longer time periods (∼ 2.3 s). A similar pattern of mobility was seen for the MR activated by aldosterone. Inactive receptors (mutant or antagonist-bound receptors) show a decreased DNA binding frequency and duration, but also a higher mobility for the diffusing population. Likely, very brief (≤ 1 ms) interactions with DNA induced by the agonists underlie this difference in diffusion behavior. Surprisingly, different agonists also induce different mobilities of both receptors, presumably due to differences in ligand-induced conformational changes and receptor complex formation. In summary, our data provide a consistent quantitative model of the dynamics of GR and MR, indicating three types of interactions with DNA, which fit into a model in which frequent low-affinity DNA binding facilitates the search for high-affinity target sequences.

Indexed as

AnimalsCell Line, TumorChlorocebus aethiopsCOS CellsDNAFluorescence Recovery After PhotobleachingHumansMicroscopyModels, TheoreticalProtein BindingReceptors, GlucocorticoidReceptors, MineralocorticoidDNAReceptors, GlucocorticoidReceptors, Mineralocorticoid

Identifiers

PMID24632838
PMCPMC3954550
OpenAlexW2069925552

What OpenQuestion holds

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LicenceCC BY
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.