Evidence map›Paper›PMID 40545232›Full record

ArticleJournal of molecular biology2025

An Intrinsically Disordered Region of Histone Demethylase KDM5A Activates Catalysis Through Interactions With the Nucleosomal Acidic Patch and DNA.

Ali M Palla, Chien-Chu Lin, Michael J Trnka, Emme M Leao, Nektaria Petronikolou, Alma L Burlingame, Robert K McGinty, Danica Galonić Fujimori

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of molecular biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Ali M PallaTETRAD Graduate Program, University of California, 600 16th Street, Genentech Hall, San Francisco, CA 94158, United States.
Chien-Chu LinDivision of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, Chapel Hill, NC 27599, United States.
Michael J TrnkaDepartment of Pharmaceutical Chemistry, University of California, 600 16th Street, Genentech Hall, San Francisco, CA 94158, United States.
Emme M LeaoUCSF SRTP Program, University of California, 600 16th Street, Genentech Hall, San Francisco, CA 94158, United States.
Nektaria PetronikolouDepartment of Cellular and Molecular Pharmacology, University of California, 600 16th Street, Genentech Hall, San Francisco, CA 94158, United States.
Alma L BurlingameDepartment of Pharmaceutical Chemistry, University of California, 600 16th Street, Genentech Hall, San Francisco, CA 94158, United States.
Robert K McGintyDivision of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, Chapel Hill, NC 27599, United States; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599 United States; Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599 United States.
Danica Galonić FujimoriDepartment of Pharmaceutical Chemistry, University of California, 600 16th Street, Genentech Hall, San Francisco, CA 94158, United States; Department of Cellular and Molecular Pharmacology, University of California, 600 16th Street, Genentech Hall, San Francisco, CA 94158, United States; Quantitative Biosciences Institute, University of California San Francisco, San Francisco, CA 94158 United States. Electronic address: Danica.Fujimori@ucsf.edu.

Funding

Molecular Mechanisms of Chromatin RecognitionR35GM133498 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Robert McGinty · 2019 to 2026
$3.3M
NIGMS NIH HHS R35 GM133498
6 · The paper itself

Abstract

Lysine demethylase 5A (KDM5A) plays a key role in the regulation of chromatin accessibility by catalyzing the removal of trimethyl marks on histone H3K4 (H3K4me3). KDM5A is also an oncogenic driver, with overexpression of KDM5A observed in various cancers, including breast, lung, and ovarian cancer. Past studies have characterized the functions of KDM5A domains, including KDM5A interactions with the histone H3 tail, but have yet to identify the broader mechanisms that drive KDM5A binding to the nucleosome. Through investigation of binding and catalysis on nucleosome substrates, we uncovered multivalent interactions of KDM5A with the H2A/H2B acidic patch and DNA that play crucial roles in the regulation of catalytic activity. We also identified an intrinsically disordered region (IDR) containing bifunctional arginine-rich motifs capable of binding to both the histone H2A/H2B acidic patch and nucleosomal DNA that is necessary for catalysis on nucleosome substrates. Our findings both elucidate previously unknown mechanisms that regulate KDM5A catalytic activity and reveal the ability of an IDR to engage in multiple interactions with chromatin.

Indexed as

Intrinsically Disordered ProteinsNucleosomesAmino Acid MotifsArginineBiotinDNAHistonesHumansProtein DomainsRetinoblastoma-Binding Protein 2ArginineBiotinDNAHistonesIntrinsically Disordered ProteinsKDM5A protein, humanNucleosomesRetinoblastoma-Binding Protein 2chromatin modifiersepigeneticsintrinsically disordered proteinsJumonji-domain-containing histone demethylaseslysine methylation

Identifiers

PMID40545232
PMCPMC12443421

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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.