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Series GSE78801 Query DataSets for GSE78801
Status Public on Feb 27, 2017
Title Heterotypic nucleosomes and PRC2 drive DIPG oncogenesis
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Diffuse intrinsic pontine gliomas (DIPG) are characterized by a heterozygous lysine-to-methionine mutation of histone H3 (H3K27M) that potently reduces Polycomb Repressive Complex 2 (PRC2) methylation of wild-type histone H3K27 (H3K27wt). The role of H3K27M and reduced H3K27wt methylation in DIPG pathogenesis has yet to be determined. Here, we have performed epigenomic profiling of patient-derived H3K27M mutant DIPG cells and demonstrate that H3K27M resides in nucleosomes with H3K27wt acetylation (H3K27ac), and H3K27M-H3K27ac containing nucleosomes co-localize with bromodomain proteins at actively transcribed genes and that PRC2 is excluded from H3K27M occupied regions. With respect to therapeutic implications of these observations, we demonstrate that pharmacologic bromodomain protein inhibition suppresses tumor growth in vivo. In total, our results indicate that H3K27M promotes H3K27ac at the expense of H3K27 methylation, and points to bromodomain protein inhibition as a clinical strategy for treating DIPG.
Overall design Examination of different histone modifications, histone mutant and chromatin modifiers in 2 different DIPG patient-derived cells. Control cells such as HCT116 were used to test H3K27M antibody specificity
Contributor(s) Piunti A, Bartom ET, Shilatifard A
Citation(s) 28263307
Submission date Mar 01, 2016
Last update date May 15, 2019
Contact name Ali Shilatifard
Organization name Northwestern University Feinberg School of Medicine
Department Department of Biochemistry and Molecular Genetics
Lab Shilatifard Lab
Street address 320 E Superior St
City Chicago
State/province IL
ZIP/Postal code 60611
Country USA
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (100)
GSM2265624 SF8628_H3K27M_rep1
GSM2265625 SF8628_H3K27M_rep2
GSM2265626 SF8628_Rna_Pol_II_rep1
BioProject PRJNA313974
SRA SRP071040

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Supplementary file Size Download File type/resource
GSE78801_RAW.tar 99.9 Gb (http)(custom) TAR (of BW)
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Raw data are available in SRA
Processed data provided as supplementary file

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