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Series GSE134445 Query DataSets for GSE134445
Status Public on Oct 19, 2022
Title The histone H3G34R mutation disrupts the epigenome via catalytic inactivation of the ASH1 H3K36 methyltransferase [ATAC-seq]
Organism Neurospora crassa
Experiment type Methylation 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 DNA methylation in Neurospora crassa strains (wild-type and four mutants) by Whole Genome Bisulfite-Seq. Biological replicates are included for wild-type and ash1(Y888F) backgrounds.
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)
GPL16164 Illumina HiSeq 2000 (Neurospora crassa)
GPL23150 Illumina HiSeq 4000 (Neurospora crassa)
Samples (5)
GSM3948522 WT_5mC
GSM3948523 ash1(Y888F)_5mC
GSM3948524 H3G34R_5mC
This SubSeries is part of SuperSeries:
GSE134452 The histone H3G34R mutation disrupts the epigenome via catalytic inactivation of the ASH1 H3K36 methyltransferase
BioProject PRJNA555417
SRA SRP215539

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE134445_RAW.tar 101.8 Mb (http)(custom) TAR (of BIGWIG, IGV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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