Evidence map›Paper›PMID 33619101›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

Depletion of H3K36me2 recapitulates epigenomic and phenotypic changes induced by the H3.3K36M oncohistone mutation.

Kartik N Rajagopalan, Xiao Chen, Daniel N Weinberg, Haifen Chen, Jacek Majewski, C David Allis, Chao Lu

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
3.2field-weighted citation impact, top 7% 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

35 citing papers in PubMed, 50 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

7 authors at 4 institutions in 2 countries.

Kartik N RajagopalanDivision of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032.
Xiao ChenDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032.ORCID 0000-0001-5059-8846
Daniel N WeinbergLaboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, NY 10065.ORCID 0000-0002-6718-3724
Haifen ChenDepartment of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada.
Jacek MajewskiDepartment of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; jacek.majewski@mcgill.ca alliscd@rockefeller.edu cl3684@cumc.columbia.edu.
C David AllisLaboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, NY 10065; jacek.majewski@mcgill.ca alliscd@rockefeller.edu cl3684@cumc.columbia.edu.ORCID 0000-0001-7589-713X
Chao LuDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032; jacek.majewski@mcgill.ca alliscd@rockefeller.edu cl3684@cumc.columbia.edu.
Columbia University Irving Medical Center · USRockefeller University · USMcGill Genome Centre · CAMcGill University · CA

Funding

Weill Cornell/Rockefeller/Sloan-Kettering MST ProgramT32GM007739 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI HSU, KATHARINE C · 1985 to 2023
$51.1M
Shared Resources Core 2: Quantitative Proteomics CoreP01CA196539 · NCI · ROCKEFELLER UNIVERSITY · PI YOUNG, MICHAEL WARREN · 2015 to 2024
$17.6M
J. NRSA Training CoreTL1TR002386 · NCATS · WEILL MEDICAL COLL OF CORNELL UNIV · PI Genevieve Giny Fouda Amou ou · 2017 to 2026
$5.8M
The Columbia University Training Program in Lung ScienceT32HL105323 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Jahar Bhattacharya, Wellington V. Cardoso · 2011 to 2026
$4.7M
Regulation and Function of Histone H3K36 Methylation in Mammalian ChromatinR35GM138181 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI LU, CHAO · 2020 to 2024
$2.0M
Perturbation of Polycomb-mediated gene repression by histone H3 mutations.F30CA224971 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI WEINBERG, DANIEL N · 2018 to 2020
$150k
CIHRNCATS NIH HHS TL1 TR002386NCI NIH HHS F30 CA224971NCI NIH HHS P01 CA196539NHLBI NIH HHS T32 HL105323NIGMS NIH HHS R35 GM138181NIGMS NIH HHS T32 GM007739
6 · The paper itself

Abstract

Hotspot histone H3 mutations have emerged as drivers of oncogenesis in cancers of multiple lineages. Specifically, H3 lysine 36 to methionine (H3K36M) mutations are recurrently identified in chondroblastomas, undifferentiated sarcomas, and head and neck cancers. While the mutation reduces global levels of both H3K36 dimethylation (H3K36me2) and trimethylation (H3K36me3) by dominantly inhibiting their respective specific methyltransferases, the relative contribution of these methylation states to the chromatin and phenotypic changes associated with H3K36M remains unclear. Here, we specifically deplete H3K36me2 or H3K36me3 in mesenchymal cells, using CRISPR-Cas9 to separately knock out the corresponding methyltransferases NSD1/2 or SETD2. By profiling and comparing the epigenomic and transcriptomic landscapes of these cells with cells expressing the H3.3K36M oncohistone, we find that the loss of H3K36me2 could largely recapitulate H3.3K36M's effect on redistribution of H3K27 trimethylation (H3K27me3) and gene expression. Consistently, knockout of

Indexed as

Epigenesis, GeneticProtein Processing, Post-TranslationalAnimalsAntimetabolites, AntineoplasticCarcinogenesisCell LineChromatinCRISPR-Cas SystemsCytarabineDecitabineGene EditingHistone-Lysine N-MethyltransferaseHistonesHumansLysineMesenchymal Stem CellsAntimetabolites, AntineoplasticChromatinCytarabineDecitabineHistone-Lysine N-MethyltransferaseHistonesLysineNeoplasm ProteinsNSD1 protein, humanNSD2 protein, humanProtein IsoformsRepressor ProteinsSETD2 protein, humancancerchromatin and epigenomicsH3K36 methylationNSDoncohistone

Identifiers

PMID33619101
PMCPMC7936350
OpenAlexW3132027188

What OpenQuestion holds

Textmetadata
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.