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GSE98761
Mus musculus
8 Downloadable Samples
Description
Histone H3 lysine 9 (H3K9) methylation is an epigenetic mark of transcriptionally repressed chromatin. During mammalian development, H3K9 methylation levels seem to be spatiotemporally regulated by the opposing activities of methyltransferases and demethylases to govern correct gene expression. However, the combination(s) of H3K9 methyltransferase(s) and demethylase(s) that contribute to this regulation and the genes regulated by them remain unclear. Herein, we demonstrate the essential roles of H3K9 demethylases Jmjd1a and Jmjd1b in the embryogenesis and viability control of embryonic stem (ES) cells. Mouse embryos lacking Jmjd1a/Jmjd1b died after implantation. Depletion of Jmjd1a/Jmjd1b in mouse ES cells induced rapid cell death accompanied with a massive increase in H3K9 methylation. Jmjd1a/Jmjd1b depletion induced an increase in H3K9 methylation in the gene-rich regions of the chromosomes, indicating that Jmjd1a/Jmjd1b removes H3K9 methylation marks in the euchromatin. Importantly, the additional disruption of the H3K9 methyltransferase G9a in a Jmjd1a/Jmjd1b-deficient background rescued not only the H3K9 hypermethylation phenotype but also the cell death phenotype. We also found that Jmjd1a/Jmjd1b removes H3K9 methylation marks deposited by G9a in the Oct4 and Ccnd1 loci to activate transcription. In conclusion, Jmjd1a/Jmjd1b ensures ES cell viability by antagonizing G9a-mediated H3K9 hypermethylation in the gene-rich euchromatin.
Publication Title
Combined Loss of JMJD1A and JMJD1B Reveals Critical Roles for H3K9 Demethylation in the Maintenance of Embryonic Stem Cells and Early Embryogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 1 Downloadable Sample
Description
Epigenetic gene regulation in various oncogenic pathways is currently an important focus of cancer research. The PI3K pathway plays a pivotal role in hepatocellular carcinoma, but the significance of histone modification in the PI3K pathway-dependent hepatotumorigenesis remains unknown.
Publication Title
Impact of histone demethylase KDM3A-dependent AP-1 transactivity on hepatotumorigenesis induced by PI3K activation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 29 Downloadable Samples
Description
Polymorphisms in the interleukin-4 receptor chain (IL-4R) have been linked to asthma incidence and severity, but a causal relationship has remained uncertain. In particular, a glutamine to arginine substitution at position 576 (Q576R) of IL-4R has been associated with severe asthma, especially in African Americans. We show that mice carrying the Q576R polymorphism exhibited intense allergen-induced airway inflammation and remodeling. The Q576R polymorphism did not affect proximal signal transducer and activator of transcription (STAT) 6 activation, but synergized with STAT6 in a gene target and tissue-specific manner to mediate heightened expression of a subset of IL-4 and IL-13responsive genes involved in allergic inflammation. Our findings indicate that the Q576R polymorphism directly promotes asthma in carrier populations by selectively augmenting IL-4Rdependent signaling.
Publication Title
Pathogenicity of a disease-associated human IL-4 receptor allele in experimental asthma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Human and mouse blood each contain two monocyte subsets. Here, we investigated the extent of their similarity using a microarray approach. Approximately 300 genes in human and 550 genes in mouse were differentially expressed between subsets. More than 130 of these gene expression differences were conserved between mouse and human monocyte subsets. We confirmed numerous differences at the cell surface protein level. Despite overall conservation, some molecules were conversely expressed between the two species subsets, including CD36, CD9, and TREM-1. Furthermore, other differences existed, including a prominent PPAR signature in mouse monocytes absent in human. Overall, human and mouse monocyte subsets are far more broadly conserved than currently recognized. Thus, studies in mice may indeed yield relevant information regarding the biology of human monocyte subsets. However, differences between the species deserve consideration in models of human disease studied in the mouse.
Publication Title
Comparison of gene expression profiles between human and mouse monocyte subsets.
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No sample metadata fields
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