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Series GSE148048 Query DataSets for GSE148048
Status Public on Mar 22, 2021
Title ChIP-seq and RNA-seq analyses in human multiple myeloma cell line MM.1S
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary Recent studies have highlighted the oncogenic roles of KDM5A; however, its molecular mechanism has not been fully delineated. Here we identifies KDM5A as a transcriptional activator of MYC target genes in multiple myeloma (MM). Genetic ablation of KDM5A or pharmacologic inhibition of KDM5 by novel inhibitor JQKD82 impairs MM cell growth. Gene expression profile reveals that JQKD82 decreases expression of MYC targets. Expression of MYC targets is similarly downregulated by KDM5A depletion, but little affected by KDM5B knockdown. Mechanistically, KDM5A co-localizes with MYC across the genome, and KDM5A and MYC coordinately promote MYC target gene transcription. The treatment with JQKD82 reduces phosphorylation level of RNA polymerase II (RNAPII), resulting in RNAPII pausing, accompanied by hyper-H3K4me3 status at the MYC loci. Finally, we shows that JQKD82 exerts anti-MM activity and prolongs overall survival in vivo mouse xenograft models. Our results delineate KDM5A function that reinforces MYC transcriptional program, and identify KDM5A as a potential therapeutic target in MM.
This SuperSeries is composed of the SubSeries listed below.
 
Overall design Refer to individual Series
 
Contributor(s) Ohguchi H, Gryder BE
Citation(s) 34258103
Submission date Apr 03, 2020
Last update date Jul 27, 2021
Contact name Hiroto Ohguchi
E-mail(s) ohguchi@kumamoto-u.ac.jp
Phone +81-96-373-6596
Organization name Kumamoto University
Department IRDA
Lab Ohguchi Lab
Street address 2-2-1 Honjo, Chuo-ku
City Kumamoto
State/province Kumamoto
ZIP/Postal code 860-0811
Country Japan
 
Platforms (2)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (34)
GSM4453030 MM.1S_INPUT(forKDM5A)_ChIP-seq
GSM4453031 MM.1S_KDM5A_ChIP-seq
GSM4453032 MM.1S_INPUT(forRNAPIISer2p5p)_DMSO_ChIPseq
This SuperSeries is composed of the following SubSeries:
GSE148046 ChIP-seq analyses for KDM5A, H3K4me3, RNAPII and TAF3 in human multiple myeloma cell line MM.1S
GSE148047 RNA-seq analysis after JQKD82 treatment in human multiple myeloma cell line MM.1S
Relations
BioProject PRJNA622952

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
GSE148048_RAW.tar 1.6 Gb (http)(custom) TAR (of BED, TDF, TXT)
SRA Run SelectorHelp

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