Evidence map›Paper›PMID 28934504›Full record

ArticleNucleic acids research2017

Accumulation of histone variant H3.3 with age is associated with profound changes in the histone methylation landscape.

Andrey Tvardovskiy, Veit Schwämmle, Stefan J Kempf, Adelina Rogowska-Wrzesinska, Ole N Jensen

Abstract read
In one paragraph

Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed, 2 pooled it
–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

75 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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15 more citing papers are in PubMed but not listed here.

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

5 authors.

Andrey TvardovskiyDepartment of Biochemistry and Molecular Biology, VILLUM Center for Bioanalytical Sciences, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
Veit SchwämmleDepartment of Biochemistry and Molecular Biology, VILLUM Center for Bioanalytical Sciences, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
Stefan J KempfDepartment of Biochemistry and Molecular Biology, VILLUM Center for Bioanalytical Sciences, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
Adelina Rogowska-WrzesinskaDepartment of Biochemistry and Molecular Biology, VILLUM Center for Bioanalytical Sciences, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
Ole N JensenDepartment of Biochemistry and Molecular Biology, VILLUM Center for Bioanalytical Sciences, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Deposition of replication-independent histone variant H3.3 into chromatin is essential for many biological processes, including development and reproduction. Unlike replication-dependent H3.1/2 isoforms, H3.3 is expressed throughout the cell cycle and becomes enriched in postmitotic cells with age. However, lifelong dynamics of H3 variant replacement and the impact of this process on chromatin organization remain largely undefined. Using quantitative middle-down proteomics we demonstrate that H3.3 accumulates to near saturation levels in the chromatin of various mouse somatic tissues by late adulthood. Accumulation of H3.3 is associated with profound changes in global levels of both individual and combinatorial H3 methyl modifications. A subset of these modifications exhibit distinct relative abundances on H3 variants and remain stably enriched on H3.3 throughout the lifespan, suggesting a causal relationship between H3 variant replacement and age-dependent changes in H3 methylation. Furthermore, the H3.3 level is drastically reduced in human hepatocarcinoma cells as compared to nontumoral hepatocytes, suggesting the potential utility of the H3.3 relative abundance as a biomarker of abnormal cell proliferation activity. Overall, our study provides the first quantitative characterization of dynamic changes in H3 proteoforms throughout lifespan in mammals and suggests a role for H3 variant replacement in modulating H3 methylation landscape with age.

Indexed as

AgingAnimalsCarcinoma, HepatocellularCells, CulturedHepatocytesHistone CodeHistonesHumansLiver NeoplasmsLysineMaleMethylationMice, Inbred C57BLProtein IsoformsProtein Processing, Post-TranslationalHistonesLysineProtein Isoforms

Identifiers

PMID28934504
PMCPMC5766163

What OpenQuestion holds

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LicenceCC BY-NC
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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.