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Series GSE35061 Query DataSets for GSE35061
Status Public on Jul 30, 2014
Title Role of the hypoxia-inducible histone H3K9 methylation regulating enzymes Jmjd1a and G9a in stem cell self-renewal and tumorigenesis
Organism Mus musculus
Experiment type Expression profiling by array
Summary Hypoxia is one of the major driving forces mediating tumor angiogenesis, aggressiveness, as well as resistance to chemo- and radiotherapy. It has also been suggested to play important roles in stem cell maintenance for both normal and cancer tissues. However, the mechanisms by which hypoxia-driven epigenetic changes modulate tumorigenesis remain poorly understood. As the histone H3 lysine 9 (H3K9) demethylase Jmjd1a and methyltransferase G9a are upregulated downstream targets of hypoxia, we focused on these two catalytically opposing epigenetic modifiers to address this question. Through the use of homozygous Jmjd1a and G9a knockout mouse embryonic stem (ES) cells, we found that Jmjd1a was not required for stem cell self-renewal and that anti-angiogenesis related genes were epigenetically dysregulated in both Jmjd1a- and G9a deficient ES cells under hypoxic conditions, accompanied by corresponding changes in H3K9 dimethylation and H3K4 trimethylation levels in the proximal promoter regions of these target genes. Most importantly, these genetic alterations led to opposing tumor phenotypes: loss of Jmjd1a results in increased tumor growth, whereas loss of G9a produces smaller tumors. These findings provide new insights on the importance of hypoxia signalling in regulating the epigenetic status and expression of angiogenesis genes that promote tumor progression.
 
Overall design 63 microarray samples consisting of 7 mouse ES cell lines of which 2 are wild type (control), 2 Jmjd1a knockout, 2 G9a knockout and 1 G9a knockout that was reconstituted for G9a (G9a control). Each cell line and condition was seeded at 3 different densities (2X10^5, 4X10^5 and 6X10^5) in 6 cm dishes to control for the effects of cell confluency on gene expression. 18 hours after plating, the cells were subjected to normoxia (21% O2) for 24 hours (control), normoxia 20 hours followed by hypoxia (1% O2) for 4 hours (acute hypoxia) and 24 hours hypoxia (chronic treatment). Total RNA was harvested from all samples for microarrays after the 24 hour treatments.
 
Contributor(s) Ueda J, Ho JC, Lee KL, Shojiro K, Yang H, Sun WD, Fukuhara N, Zaiden N, Chan SL, Tachibana M, Shinkai Y, Kato H, Poellinger L
Citation(s) 25071150
Submission date Jan 12, 2012
Last update date Jun 14, 2018
Contact name Kian Leong LEE
E-mail(s) [email protected]
Phone +(65) 6601 3685
Organization name National University of Singapore (NUS)
Department Duke-NUS Medical School
Lab Cancer & Stem Cell Biology Program (CSCB)
Street address #07-21, 8 College Road
City Singapore
State/province Singapore
ZIP/Postal code 169857
Country Singapore
 
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (63)
GSM861536 WT1 Normoxia 24h 2X10^5 cells/6cm plate
GSM861537 WT1 Normoxia 24h 4X10^5 cells/6cm plate
GSM861538 WT1 Normoxia 24h 6X10^5 cells/6cm plate
Relations
BioProject PRJNA150935

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
GSE35061_RAW.tar 3.1 Mb (http)(custom) TAR
GSE35061_non-normalized.txt.gz 10.0 Mb (ftp)(http) TXT
Processed data included within Sample table
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