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Series GSE110570 Query DataSets for GSE110570
Status Public on Sep 25, 2019
Title Re-programing chromatin with a bifunctional LSD1/HDAC inhibitor induces therapeutic differentiation in DIPG [ChIP-seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Histone H3 lysine 27 to methionine mutations (H3K27M) resulting in aberrant chromatin regulation are frequently observed in Diffuse Intrinsic Pontine Glioma (DIPG), a pediatric brain tumor with no cure. We conducted a CRISPR screen to determine if various chromatin regulators might be targeted to treat DIPG. Excitingly, this genetic screen reveals that co-targeting lysine specific demethylase 1 (LSD1) and histone deacetylases (HDACs) results in an enhanced growth suppressive effect in patient DIPG cells. Consistent with the genetic screen, a bifunctional inhibitor of HDACs and LSD1, Corin, inhibits DIPG growth in vitro and in xenografts. Mechanistically, Corin rescues H3K27me3 levels typically suppressed by the dominant effects of H3K27M mutations in DIPG and simultaneously increases HDAC-targeted H3K27ac and LSD1-targeted H3K4me1 at enhancers. Further studies reveal that Corin de-regulates DIPG transcription resulting in cell death, cell cycle arrest, and the induction of neuronal differentiation. These data suggest that co-targeting LSD1 and HDACs may represent a novel strategy for treating DIPG.
 
Overall design We performed ChIP-seq using antibodies to H3K27me3, H3K27ac, and H3K4me1 modified histones in SU-DIPGXIII diffuse intrinsic pontine glioma cells after one week of treatment with either DMSO (control) or a dual inhibitor of LSD1 and HDACs 1-3 (Corin).
 
Contributor(s) Anastas J, Shi Y
Citation(s) 31631026
Submission date Feb 13, 2018
Last update date Jan 13, 2020
Contact name Jamie Anastas
E-mail(s) jamie.anastas@childrens.harvard.edu, jamieanastas@gmail.com
Phone 16174298539
Organization name Boston Children's Hospital
Department Newborn Medicine
Lab Yang Shi
Street address 300 Longwood Ave
City Boston, MA
State/province United States of America
ZIP/Postal code 02115
Country USA
 
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (18)
GSM3003377 DMSO_SUDIPGXIII_H3K4me1_rep1
GSM3003378 DMSO_SUDIPGXIII_H3K4me1_rep2
GSM3003379 CORIN_SUDIPGXIII_H3K4me1_rep1
This SubSeries is part of SuperSeries:
GSE110572 Re-programing chromatin with a bifunctional LSD1/HDAC inhibitor induces therapeutic differentiation in DIPG
Relations
BioProject PRJNA434043
SRA SRP132826

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
GSE110570_CORIN_K27ac_track.bigwig 2.3 Gb (ftp)(http) BIGWIG
GSE110570_CORIN_K27me3_track.bigwig 1.3 Gb (ftp)(http) BIGWIG
GSE110570_CORIN_K4me1_track.bigwig 7.3 Gb (ftp)(http) BIGWIG
GSE110570_DIPGXIII_K27M_broadPeak_top5000.bed.gz 49.0 Kb (ftp)(http) BED
GSE110570_DMSO_K27ac_track.bigwig 6.8 Gb (ftp)(http) BIGWIG
GSE110570_DMSO_K27me3_track.bigwig 4.7 Gb (ftp)(http) BIGWIG
GSE110570_DMSO_K4me1_track.bigwig 9.3 Gb (ftp)(http) BIGWIG
GSE110570_RAW.tar 616.6 Mb (http)(custom) TAR (of BED, BIGWIG)
GSE110570_input_track.bigwig 7.0 Gb (ftp)(http) BIGWIG
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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