Evidence map›Paper›PMID 39605374›Full record

ArticlebioRxiv : the preprint server for biology2024

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

Kanishk Jain, Pata-Eting Kougnassoukou Tchara, Amanuel B Mengistalem, Aidan P Holland, Christopher N Bowman, Matthew R Marunde, Irina K Popova, Spencer W Cooke, Krzysztof Krajewski, Michael-Christopher Keogh and 2 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. 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

12 authors.

Kanishk JainDepartment of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Twin Cities, Minneapolis, MN, USA.ORCID 0000-0001-8039-0464
Pata-Eting Kougnassoukou TcharaDepartment of Molecular Medicine and Cancer Research Center, Université Laval, Quebec City, QC, Canada; CHU de Québec Research Center, Quebec City, QC, Canada.
Amanuel B MengistalemDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Aidan P HollandDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Christopher N BowmanDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Matthew R MarundeEpiCypher, Inc., Durham, NC, USA.
Irina K PopovaEpiCypher, Inc., Durham, NC, USA.
Spencer W CookeDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Krzysztof KrajewskiDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Michael-Christopher KeoghEpiCypher, Inc., Durham, NC, USA.
Jean-Philippe LambertDepartment of Molecular Medicine and Cancer Research Center, Université Laval, Quebec City, QC, Canada; CHU de Québec Research Center, Quebec City, QC, Canada.ORCID 0000-0002-0833-1221
Brian D StrahlDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0002-4947-6259

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
NCI NIH HHS P30 CA016086NCI NIH HHS T32 CA217824NIGMS NIH HHS R35 GM126900NIGMS NIH HHS R44 GM116584
6 · The paper itself

Abstract

Plant homeodomain (PHD) fingers are critical effectors of histone post-translational modifications (PTMs), acting as regulators of gene expression and genome integrity, and frequently presenting 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 PHD finger-containing proteins in humans remain poorly understood, despite their significant implications in disease processes. In this study, we undertook a comprehensive analysis of one such poorly characterized PHD finger-containing protein, PHRF1. Using biochemical, molecular, and cellular approaches, we show that PHRF1 robustly binds to histone H3, specifically at its N-terminal region. Through RNA-seq and proteomic analyses, we also find that PHRF1 is intricately involved in transcriptional and RNA splicing regulation and plays a significant role in DNA damage response (DDR). Crucially, mutagenesis of proline 221 to leucine (P221L) in the PHD finger of PHRF1 abolishes histone interaction and fails to rescue defective DDR. These findings underscore the importance of PHRF1-H3 interaction in maintaining genome integrity and provide insight into how PHD fingers contribute to chromatin biology.

Indexed as

DNA repairHistone H3PHD fingerPHRF1RNA splicingtranscription

Identifiers

PMID39605374
PMCPMC11601626

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.