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Series GSE134449 Query DataSets for GSE134449
Status Public on Oct 19, 2022
Title The histone H3G34R mutation disrupts the epigenome via catalytic inactivation of the ASH1 H3K36 methyltransferase [ChIP-seq]
Organism Neurospora crassa
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary The recurrent mutation of histone variant H3.3 at glycine-34 (H3.3G34) defines a type of pediatric glioma. Characteristic changes to the epigenome associated with the disease are thought to be the consequence of altered methylation of the adjacent lysine-36 (K36) residue, but the complexity of this regulatory pathway in humans, combined with a multi-component disease etiology, has limited our understanding of how H3.3G34 mutations contribute to oncogenesis. Here we use Neurospora crassa to show that the most common mutation associated with this tumor, glycine to arginine (G34R), drives aberrant heterochromatin formation and abnormal growth by inhibiting the H3K36 methyltransferase ASH1. Inactivation of ASH1, either directly or with H3G34R, drives spurious intergenic DNA methylation, redistribution of H3K27 methylation, and derepression of silent genes. We provide evidence that these defects are largely due to aberrant activity of RNA polymerase II (RNAPII)-associated SET-2, and propose targeted SET-2 inhibition as a therapeutic strategy for H3.3G34R gliomas.
Overall design We analyzed the distribution of histone H3 lysine 27 methylation (H3K27me2/3), H3K36me2/3, and H3K9me3 in Neurospora crassa by chromatin immunoprecipitation. Strains were grown, crosslinked, lysed, modified nucleosomes were immunopurified, and associated DNA was sequenced. A total of five genetic backgrounds are included here. Each background and each mark was done in replicate. Data sets with wild-type strains and related mutant backgrounds are deposited in GEO submision GSE118495.
Contributor(s) Bicocca VT, Rountree MR, Ormsby T, Selker EU
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Submission date Jul 17, 2019
Last update date Oct 22, 2022
Contact name Elizabeth Toomey Wiles
Organization name University of Oregon
Department Biology, Institute of Molecular Biology
Lab Selker
Street address 1229 University of Oregon; 1318 Franklin Blvd.
City Eugene
State/province OR
ZIP/Postal code 97403
Country USA
Platforms (2)
GPL20660 Illumina NextSeq 500 (Neurospora crassa)
GPL23150 Illumina HiSeq 4000 (Neurospora crassa)
Samples (12)
GSM3948552 H3G34R H3K36me2 ChIP-seq
GSM3948553 H3G34R_H3K36me3_ChIP-seq
GSM3948554 H3G34R_H3K27me2/3_ChIP-seq
This SubSeries is part of SuperSeries:
GSE134452 The histone H3G34R mutation disrupts the epigenome via catalytic inactivation of the ASH1 H3K36 methyltransferase
BioProject PRJNA555435
SRA SRP215548

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Supplementary file Size Download File type/resource
GSE134449_RAW.tar 313.8 Mb (http)(custom) TAR (of BIGWIG, TDF)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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