Evidence map›Paper›PMID 40671529›Full record

ArticleNucleic acids research2025

Histone H3 N-terminal recognition by the PHD finger of PHRF1 is required for proper DNA damage response.

Kanishk Jain, Pata-Eting Kougnassoukou Tchara, Abid Khan, Amanuel B Mengistalem, Aidan P Holland, Christopher N Bowman, Matthew R Marunde, Tiffany A Engel, Irina K Popova, Spencer W Cooke and 4 more

Abstract read
In one paragraph

Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Kanishk JainDepartment of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Twin Cities, Minneapolis, MN 55455, United States.ORCID 0000-0001-8039-0464
Pata-Eting Kougnassoukou TcharaEndocrinology and nephrology Research program, CHU de Québec-Université Laval Research Center; Department of Molecular Medicine, Cancer Research Centre, Université Laval, Québec, QCG1V 4G2, Canada.
Abid KhanDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
Amanuel B MengistalemDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
Aidan P HollandDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
Christopher N BowmanDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
Matthew R MarundeEpiCypher, Inc., Durham, NC 27709, United States.ORCID 0009-0007-5934-7200
Tiffany A EngelDepartment of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Twin Cities, Minneapolis, MN 55455, United States.
Irina K PopovaEpiCypher, Inc., Durham, NC 27709, United States.ORCID 0009-0006-8612-3264
Spencer W CookeDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
Krzysztof KrajewskiDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
Michael-Christopher KeoghEpiCypher, Inc., Durham, NC 27709, United States.ORCID 0000-0002-2219-8623
Jean-Philippe LambertEndocrinology and nephrology Research program, CHU de Québec-Université Laval Research Center; Department of Molecular Medicine, Cancer Research Centre, Université Laval, Québec, QCG1V 4G2, Canada.
Brian D StrahlDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
Mechanisms of chromatin and transcriptional regulationR35GM126900 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Brian D Strahl · 2018 to 2026
$5.5M
Cancer Epigenetics Training GrantT32CA217824 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WEISSMAN, BERNARD E. · 2017 to 2021
$1.8M
Barcoded nucleosomes for analyzing combinatorial epigenetic regulatorsR44GM116584 · NIGMS · EPICYPHER, INC. · PI SUN, ZU-WEN · 2017 to 2018
$1.6M
American Cancer Society PF-20-149-01-DMCBourse de formation Desjardins pour la recherche et l'innovationCancer Research Centre - Université LavalEpiCypher R35GM126900EpiCypher R44GM116584Fondation CHU de Québec, a Bourse Distinction Luc BélangerFonds de Recherche du Québec-Santé FRQS; 312369NCI NIH HHS P30 CA016086NCI NIH HHS T32 CA217824NIGMS NIH HHS R35 GM126900NIGMS NIH HHS R44 GM116584NIH HHS T32CA217824UNC Lineberger Cancer Center
6 · The paper itself

Abstract

Plant homeodomain (PHD) fingers are critical effectors of histone post-translational modifications (PTMs), regulating gene expression and genome integrity, and are frequently implicated in human disease. While most PHD fingers recognize unmodified and methylated states of histone H3 lysine 4 (H3K4), the specific functions of many of the over 100 human PHD finger-containing proteins are poorly understood. Here, we present a comprehensive analysis of one such poorly characterized PHD finger-containing protein, PHRF1. Using biochemical, molecular, and cellular approaches, we demonstrate that PHRF1 robustly binds to histone H3, specifically at its N-terminal region. Through integrating RNA-seq and proteomic analyses, we show that PHRF1 regulates transcription and RNA splicing and plays a critical role in DNA damage response (DDR). Crucially, we show that a cancer-associated mutation in the PHRF1 PHD finger (P221L) abolishes its histone interaction and fails to rescue defective DDR in PHRF1 knockout cells. These findings underscore the importance of the PHRF1-H3 interaction in maintaining genome integrity and provide new insight into how PHD fingers contribute to chromatin biology.

Indexed as

DNA DamageDNA RepairHistonesPHD Zinc FingersChromatinHEK293 CellsHumansMutationProtein BindingRNA SplicingChromatinHistones

Identifiers

PMID40671529
PMCPMC12266144

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.