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Title: Role of the hypoxia-inducible histone H3K9 methylation regulating enzymes Jmjd1a and G9a in stem cell self-renewal and tumorigenesis      
dateReleased:
07-30-2014
description:
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. 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.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-35061
refinement:
raw
alternateIdentifiers:
35061
keywords:
functional genomics
dateModified:
08-02-2014
availability:
available
types:
gene expression
name:
Mus musculus
ID:
A-MEXP-1174
name:
Illumina MouseRef-8 v2.0 Expression BeadChip
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-35061/E-GEOD-35061.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-35061/E-GEOD-35061.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE35061
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress
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