Evidence map›Paper›PMID 25686748›Full record

ArticleNature communications2015

Histone demethylase KDM5A is regulated by its reader domain through a positive-feedback mechanism.

Idelisse Ortiz Torres, Kristopher M Kuchenbecker, Chimno I Nnadi, Robert J Fletterick, Mark J S Kelly, Danica Galonić Fujimori

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed
5.1field-weighted citation impact, top 4% 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

87 citing papers in PubMed, 122 citations in OpenAlex.

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  17. Gastric Cancer in the Era of Epigenetics.International journal of molecular sciences · 2024
    Review
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  20. Review

27 more citing papers are in PubMed but not listed here.

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

6 authors at 1 institution in 1 country.

Idelisse Ortiz Torres1] Department of Cellular and Molecular Pharmacology, University of California, 600 16th Street, Genentech Hall, San Francisco, California 94158, USA [2] Chemistry and Chemical Biology Graduate Program, University of California, 600 16th Street, Genentech Hall, San Francisco, California 94158, USA.
Kristopher M Kuchenbecker1] Department of Biochemistry and Biophysics, University of California, 600 16th Street, Genentech Hall, San Francisco, California 94158, USA [2] Biophysics Graduate Program, University of California, 600 16th Street, Genentech Hall, San Francisco, California 94158, USA.
Chimno I Nnadi1] Department of Cellular and Molecular Pharmacology, University of California, 600 16th Street, Genentech Hall, San Francisco, California 94158, USA [2] Chemistry and Chemical Biology Graduate Program, University of California, 600 16th Street, Genentech Hall, San Francisco, California 94158, USA [3] UCSF Medical Scientist Training Program, University of California, 513 Parnassus Avenue, San Francisco, California 94143, USA.
Robert J FletterickDepartment of Biochemistry and Biophysics, University of California, 600 16th Street, Genentech Hall, San Francisco, California 94158, USA.
Mark J S KellyDepartment of Pharmaceutical Chemistry, University of California, 600 16th Street, Genentech Hall, San Francisco, California 94158, USA.
Danica Galonić Fujimori1] Department of Cellular and Molecular Pharmacology, University of California, 600 16th Street, Genentech Hall, San Francisco, California 94158, USA [2] Department of Pharmaceutical Chemistry, University of California, 600 16th Street, Genentech Hall, San Francisco, California 94158, USA.
University of California, San Francisco · US

Funding

STRUCTURAL BIOLOGY TRAINING PROGRAMT32GM008284 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KORTEMME, TANJA · 1988 to 2022
$10.1M
NIGMS NIH HHS T32 GM008284
6 · The paper itself

Abstract

The retinoblastoma binding protein KDM5A removes methyl marks from lysine 4 of histone H3 (H3K4). Misregulation of KDM5A contributes to the pathogenesis of lung and gastric cancers. In addition to its catalytic jumonji C domain, KDM5A contains three PHD reader domains, commonly recognized as chromatin recruitment modules. It is unknown whether any of these domains in KDM5A have functions beyond recruitment and whether they regulate the catalytic activity of the demethylase. Here using biochemical and nuclear magnetic resonance (NMR)-based structural studies, we show that the PHD1 preferentially recognizes unmethylated H3K4 histone tail, product of KDM5A-mediated demethylation of tri-methylated H3K4 (H3K4me3). Binding of unmodified H3 peptide to the PHD1 stimulates catalytic domain-mediated removal of methyl marks from H3K4me3 peptide and nucleosome substrates. This positive-feedback mechanism--enabled by the functional coupling between a reader and a catalytic domain in KDM5A--suggests a model for the spread of demethylation on chromatin.

Indexed as

Gene Expression Regulation, NeoplasticAlgorithmsAmino Acid SequenceAnimalsCatalytic DomainCell LineChromatinCircular DichroismGlutathione TransferaseHumansHypoxia-Inducible Factor-Proline DioxygenasesInsectaKineticsLysineMagnetic Resonance SpectroscopyMolecular Sequence DataChromatinEGLN2 protein, humanGlutathione TransferaseHypoxia-Inducible Factor-Proline DioxygenasesKDM5A protein, humanLysineNucleosomesPeptidesRecombinant ProteinsRetinoblastoma-Binding Protein 2

Identifiers

PMID25686748
PMCPMC5080983
OpenAlexW2075552693

What OpenQuestion holds

Textmetadata
LicenceTDM
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.