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Series GSE60626 Query DataSets for GSE60626
Status Public on Aug 21, 2015
Title Activation of the Integrated Stress Response by a Jumonji Histone Demethylase Inhibitor Induces Pro-Apoptotic Metabolic Reprogramming in Multiple Myeloma
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Regulation of gene expression by chromatin modification through methylation of histone lysine residues is a dynamic, reversible process that when deregulated is associated with cancer development. In multiple myeloma, combined inhibition of the histone demethylases JARID1B, UTX and JmjD3 by the small molecule GSK-J4 prevents cellular glutamine utilization leading to amino acids deprivation, activates the integrated stress response via GCN2-dependent ATF4 activation, and induces apoptosis. This response is associated with a profound upregulation of metallothionein genes. Combined with clinical data demonstrating that overexpression of JARID1B is associated with shorter survival in multiple myeloma patients, this study highlights histone demethylases as epigenetic drug targets and places this demethylase inhibitor chemotype as having unique potential relative to established anti-myeloma treatment options.
Overall design In total there are 7 different samples analyzed and one input control. Treatments are carried out with the demethylase inhibitor (or DMSO as negative control) at 6h and 48h, or with LNA targeting demethylases (or scrambled LNA) at 7 days. A negative control at 0h is included.
Contributor(s) Pliuskys L, Hookway E, Lari F, Cain P, Pawlyn C, Reed M, Brotherton D, Davies F, Tumber A, Che K, Mazitschek R, Kucukkose C, Koca D, Gulacti F, Martinez F, Thinnes CC, Novak R, Schofield CJ, Korr D, Mund C, Wilson D, Prinjha R, Edwards CM, Gallone G, Ponting CP, Brennan PE, Bunnage M, O’Mahony A, Gronemeyer H, Günther UL, Lindow M, Ørum H, Obad S, Morgan G, Athanasou N, Christianson JC, Oppermann U
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Submission date Aug 21, 2014
Last update date May 15, 2019
Contact name Laurynas Pliuskys
Organization name University of Oxford
Department NDORMS
Lab Professor Udo Oppermann Lab
Street address Windmill Rd
City Oxford
ZIP/Postal code OX3 7LD
Country United Kingdom
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (8)
GSM1483892 input
GSM1483893 0h
GSM1483894 6h DMSO
BioProject PRJNA258666
SRA SRP045686

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

Supplementary file Size Download File type/resource
GSE60626_RAW.tar 1.2 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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