Evidence map›Paper›PMID 37873347›Full record

ArticlebioRxiv : the preprint server for biology2023

The H3.3 K36M oncohistone disrupts the establishment of epigenetic memory through loss of DNA methylation.

Joydeb Sinha, Jan F Nickels, Abby R Thurm, Connor H Ludwig, Bella N Archibald, Michaela M Hinks, Jun Wan, Dong Fang, Lacramioara Bintu

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. 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, 5 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 3 countries.

Joydeb SinhaDepartment of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Jan F NickelsNiels Bohr Institute, University of Copenhagen, Copenhagen 2100, Denmark.
Abby R ThurmBiophysics Program, Stanford University, Stanford, CA 94305, USA.
Connor H LudwigDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Bella N ArchibaldDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Michaela M HinksDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Jun WanDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Dong FangLife Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Lacramioara BintuDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Stanford University · USUniversity of Copenhagen · DKZhejiang University · CN

Funding

Medical Scientist Training ProgramT32GM145402 · NIGMS · STANFORD UNIVERSITY · PI Katrin F. Chua · 2022 to 2026
$10.0M
Live-cell multiplex super-resolution imaging of chromatin state transitionsU01DK127419 · NIDDK · STANFORD UNIVERSITY · PI BINTU, LACRAMIOARA, BOETTIGER, ALISTAIR N. · 2020 to 2024
$5.3M
Molecular Pharmacology Training GrantT32GM113854 · NIGMS · STANFORD UNIVERSITY · PI MOCHLY-ROSEN, DARIA · 2015 to 2019
$1.1M
NIDDK NIH HHS U01 DK127419NIGMS NIH HHS T32 GM113854NIGMS NIH HHS T32 GM145402
6 · The paper itself

Abstract

Histone H3.3 is frequently mutated in cancers, with the lysine 36 to methionine mutation (K36M) being a hallmark of chondroblastomas. While it is known that H3.3K36M changes the cellular epigenetic landscape, it remains unclear how it affects the dynamics of gene expression. Here, we use a synthetic reporter to measure the effect of H3.3K36M on silencing and epigenetic memory after recruitment of KRAB: a member of the largest class of human repressors, commonly used in synthetic biology, and associated with H3K9me3. We find that H3.3K36M, which decreases H3K36 methylation, leads to a decrease in epigenetic memory and promoter methylation weeks after KRAB release. We propose a new model for establishment and maintenance of epigenetic memory, where H3K36 methylation is necessary to convert H3K9me3 domains into DNA methylation for stable epigenetic memory. Our quantitative model can inform oncogenic mechanisms and guide development of epigenetic editing tools.

Identifiers

PMID37873347
PMCPMC10592807
OpenAlexW4387642601

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.