Evidence map›Paper›PMID 42884018›Full record

ArticleInternational journal of molecular sciences2026

The Catalytically Inactive KDM5B-NTT Isoform Associates with Chromatin and Increases H3K4 Trimethylation in Breast Cancer Cells.

Valeria Manzini, Elena Di Nisio, Alessandro Piana, Valerio Perticaroli, Italia Anna Asteriti, Federica Polverino, Rodolfo Negri, Valerio Licursi

Abstract read
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Article in International journal of molecular sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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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

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Valeria ManziniDepartment of Biology and Biotechnologies "C. Darwin", Sapienza University of Rome, 00185 Rome, Italy.ORCID 0000-0002-2224-3594
Elena Di NisioDepartment of Biology and Biotechnologies "C. Darwin", Sapienza University of Rome, 00185 Rome, Italy.ORCID 0000-0001-7295-3941
Alessandro PianaDepartment of Biology and Biotechnologies "C. Darwin", Sapienza University of Rome, 00185 Rome, Italy.
Valerio PerticaroliDepartment of Biology and Biotechnologies "C. Darwin", Sapienza University of Rome, 00185 Rome, Italy.
Italia Anna AsteritiInstitute of Molecular Biology and Pathology (IBPM), National Research Council (CNR) of Italy, 00185 Rome, Italy.ORCID 0000-0002-6582-5500
Federica PolverinoInstitute of Molecular Biology and Pathology (IBPM), National Research Council (CNR) of Italy, 00185 Rome, Italy.ORCID 0000-0002-0048-6122
Rodolfo NegriDepartment of Biology and Biotechnologies "C. Darwin", Sapienza University of Rome, 00185 Rome, Italy.ORCID 0000-0002-4806-7090
Valerio LicursiInstitute of Molecular Biology and Pathology (IBPM), National Research Council (CNR) of Italy, 00185 Rome, Italy.

Funding

Italian Association for Cancer Research ID 29699-2023National Research Council DSB.AD006.371-InvAt-FOE2022Sapienza University of Rome AR12419077D9BBC5Sapienza University of Rome AR125199C3952C97Sapienza University of Rome RM125199A478C772
6 · The paper itself

Abstract

Histone lysine demethylases are mainly known as transcriptional regulators for their demethylase activity, but catalysis-independent functions are increasingly recognized. This work focuses on lysine-specific demethylase 5B (KDM5B), targeting H3K4me3. The canonical functional isoform is PLU-1. A catalytically inactive N-terminally truncated isoform (NTT) was previously identified in human cell lines. NTT lacks the Jumonji N-terminal (JmjN) domain, responsible for demethylase activity, and part of the AT-Rich Interaction Domain (ARID), but retains the plant homeodomains (PHDs) involved in chromatin interaction. The study aimed to investigate NTT chromatin association, its potential regulatory role, and its phenotypic effects. NTT-FLAG was overexpressed in MCF7 cells, using PLU-1-FLAG and empty vector for comparison. Chromatin association and H3K4me3 distribution were analyzed by Cleavage Under Targets and Release Using Nuclease (CUT&RUN), while migration and invasion were assessed by wound-healing, live-imaging microscopy, and invasion assays. NTT-FLAG and PLU-1-FLAG displayed similar genomic localization, preferentially associating with active promoters enriched in H3K4me3. Both isoforms increased promoter-associated H3K4me3, suggesting that chromatin binding alone is insufficient to promote demethylation. Functionally, NTT overexpression was associated with increased directional migration and invasive capacity compared with PLU-1. Overall, these findings support a catalysis-independent regulatory role for NTT and suggest a model in which chromatin interaction is driven by PHD domains, while co-interactor availability may be required for proper PLU-1 demethylase activity.

Indexed as

Breast NeoplasmsChromatinHistonesJumonji Domain-Containing Histone DemethylasesNuclear ProteinsRepressor ProteinsCell Line, TumorCell MovementFemaleGene Expression Regulation, NeoplasticHumansMCF-7 CellsMethylationPromoter Regions, GeneticProtein IsoformsChromatinhistone H3 trimethyl Lys4HistonesJumonji Domain-Containing Histone DemethylasesKDM5B protein, humanNuclear ProteinsProtein IsoformsRepressor Proteinscancer epigeneticscell invasioncell migrationhistone modificationsKDM5BMCF7protein isoforms

Identifiers

PMID42884018
PMCPMC13664838

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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.