Evidence map›Paper›PMID 37219077›Full record

ArticleeLife2023

Identification of epigenetic modulators as determinants of nuclear size and shape.

Andria C Schibler, Predrag Jevtic, Gianluca Pegoraro, Daniel L Levy, Tom Misteli

Open access · goldAbstract read
In one paragraph

Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
6.9field-weighted citation impact, top 2% of its field
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

33 citing papers in PubMed, 45 citations in OpenAlex.

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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

5 authors at 2 institutions in 1 country.

Andria C Schibler *National Cancer Institute, Bethesda, United States.
Predrag Jevtic *Department of Molecular Biology, University of Wyoming, Laramie, United States.ORCID 0000-0003-3978-5311
Gianluca PegoraroHigh Throughput Imaging Facility (HiTIF), National Cancer Institute, NIH, Bethesda, United States.ORCID 0000-0003-2843-9464
Daniel L LevyDepartment of Molecular Biology, University of Wyoming, Laramie, United States.ORCID 0000-0002-7853-3275
Tom MisteliNational Cancer Institute, Bethesda, United States.ORCID 0000-0003-3530-3020
University of Wyoming · USHigh Throughput Biology (United States) · US

Funding

Wyoming INBRE Phase 4- Equipment Supplement for x-ray diffractometer for Center for Advanced Scientific InstrumentationP20GM103432 · NIGMS · UNIVERSITY OF WYOMING · PI Nicolas A. Blouin · 2012 to 2026
$56.8M
Nuclear Architecture and DiseaseZIABC010309 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI MISTELI, THOMAS A · 2009 to 2025
$39.8M
HiTIF Microscopy Core FacilityZICBC011567 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI PEGORARO, GIANLUCA · 2014 to 2025
$15.8M
Nuclear architecture and gene expression Z01BC010309 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI MISTELI, THOMAS A · 1999 to 2008
$3.6M
Mechanisms of nuclear size regulationR35GM134885 · NIGMS · UNIVERSITY OF WYOMING · PI Daniel Leon Levy · 2020 to 2026
$2.5M
Intramural NIH HHS Z01 BC010309Intramural NIH HHS ZIC BC011567NIGMS NIH HHS P20 GM103432NIGMS NIH HHS R35 GM134885NIH HHS NIH 1-ZIA-BC010309-23NIH HHS NIH 1-ZIC-BC011567-08NIH HHS NIH P20GM103432NIH HHS NIH R35GM134885
6 · The paper itself

Abstract

The shape and size of the human cell nucleus is highly variable among cell types and tissues. Changes in nuclear morphology are associated with disease, including cancer, as well as with premature and normal aging. Despite the very fundamental nature of nuclear morphology, the cellular factors that determine nuclear shape and size are not well understood. To identify regulators of nuclear architecture in a systematic and unbiased fashion, we performed a high-throughput imaging-based siRNA screen targeting 867 nuclear proteins including chromatin-associated proteins, epigenetic regulators, and nuclear envelope components. Using multiple morphometric parameters, and eliminating cell cycle effectors, we identified a set of novel determinants of nuclear size and shape. Interestingly, most identified factors altered nuclear morphology without affecting the levels of lamin proteins, which are known prominent regulators of nuclear shape. In contrast, a major group of nuclear shape regulators were modifiers of repressive heterochromatin. Biochemical and molecular analysis uncovered a direct physical interaction of histone H3 with lamin A mediated via combinatorial histone modifications. Furthermore, disease-causing lamin A mutations that result in disruption of nuclear shape inhibited lamin A-histone H3 interactions. Oncogenic histone H3.3 mutants defective for H3K27 methylation resulted in nuclear morphology abnormalities. Altogether, our results represent a systematic exploration of cellular factors involved in determining nuclear morphology and they identify the interaction of lamin A with histone H3 as an important contributor to nuclear morphology in human cells.

Indexed as

HistonesLamin Type ACell NucleusEpigenesis, GeneticHumansNuclear EnvelopeNuclear ProteinsHistonesLamin Type ANuclear Proteinschromosomesgene expressionhistoneshumanlaminsnucleus

Identifiers

PMID37219077
PMCPMC10259489
OpenAlexW4377564825

What Socratic holds

Textmetadata
LicenceCC0
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 Socratic graph.