Evidence map›Paper›PMID 39660649›Full record

ArticleNucleic acids research2025

Hypoxia increases methylated histones to prevent histone clipping and heterochromatin redistribution during Raf-induced senescence.

Soojeong Chang, Ramhee Moon, Dowoon Nam, Sang-Won Lee, Insoo Yoon, Dong-Sung Lee, Seunghyuk Choi, Eunok Paek, Daehee Hwang, Junho K Hur and 3 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 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
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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

13 authors.

Soojeong ChangDepartment of Life Science, University of Seoul, Seoul 02504, Republic of Korea.ORCID 0000-0002-1961-6687
Ramhee MoonDepartment of Life Science, University of Seoul, Seoul 02504, Republic of Korea.
Dowoon NamDepartment of Chemistry, Korea University, Seoul 02841, Republic of Korea.
Sang-Won LeeDepartment of Chemistry, Korea University, Seoul 02841, Republic of Korea.
Insoo YoonDepartment of Life Science, University of Seoul, Seoul 02504, Republic of Korea.
Dong-Sung LeeDepartment of Life Science, University of Seoul, Seoul 02504, Republic of Korea.
Seunghyuk ChoiDepartment of Computer Science, Hanyang University, Seoul 04763, Republic of Korea.ORCID 0000-0001-6558-9379
Eunok PaekDepartment of Computer Science, Hanyang University, Seoul 04763, Republic of Korea.ORCID 0000-0003-3655-9749
Daehee HwangSchool of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea.
Junho K HurDepartment of Genetics, College of Medicine, Hanyang University, Seoul 04763, Republic of Korea.
Youhyun NamDepartment of Applied Chemistry, University of Seoul, Seoul 02504, Republic of Korea.
Rakwoo ChangDepartment of Applied Chemistry, University of Seoul, Seoul 02504, Republic of Korea.
Hyunsung ParkDepartment of Life Science, University of Seoul, Seoul 02504, Republic of Korea.ORCID 0000-0002-6890-428X

Funding

Institute for Information and Communications Technology Promotion IITP2022-0-006240101005National Research Foundation of Korea NRF-2018R1A4A1025985
6 · The paper itself

Abstract

Hypoxia enhances histone methylation by inhibiting oxygen- and α-ketoglutarate-dependent demethylases, resulting in increased methylated histones. This study reveals how hypoxia-induced methylation affects histone clipping and the reorganization of heterochromatin into senescence-associated heterochromatin foci (SAHF) during oncogene-induced senescence (OIS) in IMR90 human fibroblasts. Notably, using top-down proteomics, we discovered specific cleavage sites targeted by Cathepsin L (CTSL) in H3, H2B and H4 during Raf activation, identifying novel sites in H2B and H4. Hypoxia counteracts CTSL-mediated histone clipping by promoting methylation without affecting CTSL's activity. This increase in methylation under hypoxia protects against clipping, reshaping the epigenetic landscape and influencing chromatin accessibility, as shown by ATAC-seq analysis. These insights underscore the pivotal role of hypoxia-induced histone methylation in protecting chromatin from significant epigenetic shifts during cellular aging.

Indexed as

Cellular SenescenceHeterochromatinHistonesCathepsin LCell HypoxiaCell LineEpigenesis, GeneticFibroblastsHumansMethylationCathepsin LHeterochromatinHistones

Identifiers

PMID39660649
PMCPMC11797049

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Registered trials

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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.