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Series GSE94834 Query DataSets for GSE94834
Status Public on Jul 02, 2018
Title H3.3K27M mutant proteins reprogram epigenome by sequestering the PRC2 complex to poised enhancers
Organisms Homo sapiens; Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Expression of histone H3.3K27M mutant proteins in diffuse intrinsic pontine glioma (DIPG) results in a global reduction of tri-methylation of H3K27 (H3K27me3), and paradoxically, H3K27me3 peaks remain at hundreds of genomic loci, a dichotomous change that lacks mechanistic insights. Here we show that the PRC2 complex is sequestered at poised enhancers, but not at active promoters with high levels of H3.3K27M proteins, thereby contributing to the global reduction of H3K27me3. Moreover, the levels of H3.3K27M proteins are low at the retained H3K27me3 peaks and consequently having minimal effects on the PRC2 activity at these loci. H3K27me3-mediated silencing at specific tumor suppressor genes, including Wilms Tumor 1, promotes proliferation of DIPG cells. These results support a model in which the PRC2 complex is redistributed to poised enhancers in H3.3K27M mutant cells and supports the proliferation of DIPG cells in part through silencing of tumor suppressor gene WT1.
Overall design To analyze how H3K27me3 are altered throughout the epigenome in H3.3K27M mutant cells, we performed H3K27me3, H3.3K27M, and EZH2 ChIP-seq in SF7761 and SF8628 cell lines and tissue samples. To gain further insight into the impact of H3.3K27M mutant proteins on H3K27me3, we also introduce the same heterozygous mutation at the H3F3A gene in mouse embryonic stem cells (ES) using the CRISPR/Cas9 genome editing technology. And performed H3K27me3, H3.3K27M, and EZH2 ChIP-seq in WT and H3.3K27M mouse embryonic stem cells.
Contributor(s) Fang D, Gan H, Lee JH, Zhou H, Sarkaria J, Zhang Z
Citation(s) 29932419
Submission date Feb 13, 2017
Last update date May 15, 2019
Contact name zhiguo zhang
Phone 212-851-4936
Organization name Columbia University
Department Pediatric and Genetics and Development
Lab Irving Cancer Research Center
Street address 1130 St. Nicholas Avenue
City New York
State/province NY
ZIP/Postal code 10032
Country USA
Platforms (2)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (43)
GSM2486295 SF7761 input
GSM2486296 SF8628 input
GSM2486297 SF7761 H3.3K27M ChIP-seq repeat 1
BioProject PRJNA374553
SRA SRP099449

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
GSE94834_RAW.tar 5.0 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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