Evidence map›Paper›PMID 35590427›Full record

ArticleEpigenetics & chromatin2022

Histone H3.3 K27M chromatin functions implicate a network of neurodevelopmental factors including ASCL1 and NEUROD1 in DIPG.

Nichole A Lewis, Rachel Herndon Klein, Cailin Kelly, Jennifer Yee, Paul S Knoepfler

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Epigenetics & chromatin, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
3.5field-weighted citation impact, top 6% 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

15 citing papers in PubMed, 24 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.

Nichole A LewisDepartment of Cell Biology and Human Anatomy, University of California Davis School of Medicine, Sacramento, CA, 95817, USA.
Rachel Herndon KleinDepartment of Cell Biology and Human Anatomy, University of California Davis School of Medicine, Sacramento, CA, 95817, USA.
Cailin KellyDepartment of Cell Biology and Human Anatomy, University of California Davis School of Medicine, Sacramento, CA, 95817, USA.
Jennifer YeeDepartment of Cell Biology and Human Anatomy, University of California Davis School of Medicine, Sacramento, CA, 95817, USA.
Paul S KnoepflerDepartment of Cell Biology and Human Anatomy, University of California Davis School of Medicine, Sacramento, CA, 95817, USA. knoepfler@ucdavis.edu.ORCID 0000-0001-5444-334X
University of California, Davis · USShriners Hospitals for Children - Erie · US

Funding

Targeting the Mutant H3.3 Pathway in GliomaR01NS106878 · NINDS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI KNOEPFLER, PAUL S · 2018 to 2022
$2.1M
NINDS NIH HHS R01 NS106878
6 · The paper itself

Abstract

backgroundThe histone variant H3.3 K27M mutation is a defining characteristic of diffuse intrinsic pontine glioma (DIPG)/diffuse midline glioma (DMG). This histone mutation is responsible for major alterations to histone H3 post-translational modification (PTMs) and subsequent aberrant gene expression. However, much less is known about the effect this mutation has on chromatin structure and function, including open versus closed chromatin regions as well as their transcriptomic consequences.

resultsRecently, we developed isogenic CRISPR-edited DIPG cell lines that are wild-type for histone H3.3 that can be compared to their matched K27M lines. Here we show via ATAC-seq analysis that H3.3K27M glioma cells have unique accessible chromatin at regions corresponding to neurogenesis, NOTCH, and neuronal development pathways and associated genes that are overexpressed in H3.3K27M compared to our isogenic wild-type cell line. As to mechanisms, accessible enhancers and super-enhancers corresponding to increased gene expression in H3.3K27M cells were also mapped to genes involved in neurogenesis and NOTCH signaling, suggesting that these pathways are key to DIPG tumor maintenance. Motif analysis implicates specific transcription factors as central to the neuro-oncogenic K27M signaling pathway, in particular, ASCL1 and NEUROD1.

conclusionsAltogether our findings indicate that H3.3K27M causes chromatin to take on a more accessible configuration at key regulatory regions for NOTCH and neurogenesis genes resulting in increased oncogenic gene expression, which is at least partially reversible upon editing K27M back to wild-type.

Indexed as

Brain Stem NeoplasmsGliomaBasic Helix-Loop-Helix ProteinsChromatinHistonesHumansMutationASCL1 protein, humanBasic Helix-Loop-Helix ProteinsChromatinHistonesNEUROD1 protein, humanASCL1ATAC-seqdiffuse midline gliomaDIPGEpigeneticsH3.3K27MNEUROD1Open chromatinSuper-enhancersTranscription factor binding motifs

Identifiers

PMID35590427
PMCPMC9121554
OpenAlexW4280600504

What OpenQuestion holds

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LicenceCC BY
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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.