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GSE23306
Mus musculus
4 Downloadable Samples
Description
Polarization of macrophages to M1 or M2 cells is important for mounting responses against bacterial and helminth infection respectively. Jumonji domain containing 3 (JMJD3), a histone 3 K27 demethylase, has been implicated in the activation of macrophages. Here we show that JMJD3 is essential for M2 macrophage polarization to helminth infection and chitin, though JMJD3 is dispensable for M1 responses. Furthermore, Jmjd3 is critical for proper bone marrow macrophage differentiation in a demethylase activity-dependent manner. Jmjd3 deficiency affected trimethylation of H3K27 in only a limited numbers of genes. Among them, we identified Irf4 as the target transcription factor critical for controlling M2 macrophage polarization. Collectively, these results show that JMJD3-mediated H3K27 demethylation is critical for regulating M2 macrophage development leading to anti-helminth host responses.
Publication Title
The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 1 Downloadable Sample
Description
This array set was used to identify the genes that are highly expressed in the mouse suprachiasmatic nucleus (SCN). Because pharmacological inhibition of Gai/o activity with pertussis toxin hampers intercellular synchronization and causes dampened rhythms of the entire SCN, we hypothesized that member(s) of the Regulator of G protein Signaling (RGS) family might contribute to synchronized cellular oscillations in the SCN. To test this hypothesis, we surveyed all known mouse Rgs genes for their expression by using GeneChip and selected the genes that are highly expressed in the SCN for further analysis.
Publication Title
Circadian regulation of intracellular G-protein signalling mediates intercellular synchrony and rhythmicity in the suprachiasmatic nucleus.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Treatment, Time
View Samples- Mus musculus
- 102 Downloadable Samples
Description
The adult mammalian brain is composed of distinct regions that have specialized roles. To dissect molecularly this complex structure, we conducted a project, named the BrainStars (B*) project, in which we sampled ~50 small brain regions, including sensory centers and centers for motion, time, memory, fear, and feeding. To avoid confusion from temporal differences in gene expression, we sampled each region every 4 hours for 24 hours, and pooled the sample sets for DNA-microarray assays. Therefore, we focused only on spatial differences in gene expression. We then used informatics to identify candidates for (1) genes with high or low expression in specific regions, (2) switch-like genes with bimodal or multimodal expression patterns, and (3) genes with a uni-modal expression pattern that exhibit stable or variable levels of expression across brain regions. We used our findings to develop an integrated database (http://brainstars.org/) for exploring genome-wide expression in the adult mouse brain.
Publication Title
Quantitative expression profile of distinct functional regions in the adult mouse brain.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 45 Downloadable Samples
Description
Living organisms detect seasonal changes in day length (photoperiod), and alter their physiological functions accordingly, to fit seasonal environmental changes. This photoperiodic system is implicated in seasonal affective disorders and the season-associated symptoms observed in bipolar disease and schizophrenia. Thyroid-stimulating hormone beta subunit (Tshb), induced in the pars tuberalis (PT), plays a key role in the pathway that regulates animal photoperiodism. However, the upstream inducers of Tshb expression remain unknown. Here we show that late-night light stimulation acutely triggers the Eya3-Six1 pathway, which directly induces Tshb expression. Using melatonin-proficient CBA/N mice, which preserve the photoperiodic Tshb-expression response, we performed a genome-wide expression analysis of the PT under chronic short-day and long-day conditions. These data comprehensively identified long-day and short-day genes, and indicated that late-night light stimulation induces long-day genes. We verified this by advancing and extending the light period by 8 hours, which acutely induced Tshb expression, within one day. In a genome-wide expression analysis under this condition, we searched for candidate upstream genes by looking for expression that preceded Tshbs, and identified Eya3 gene. These results elucidate the comprehensive transcriptional photoperiodic response in the PT, revealing the complex regulation of Tshb expression and unexpectedly rapid response to light changes in the mammalian photoperiodic system.
Publication Title
Acute induction of Eya3 by late-night light stimulation triggers TSHβ expression in photoperiodism.
Sample Metadata Fields
Sex, Age, Specimen part, Time
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Epigenetically silenced Ink4a-Arf locus is activated by loss of H3K27me3 in cellular senescence, where secreted factor expression is also involved. Here we analyzed epigenome and transcriptome alteration during Ras-induced senescence using mouse embryonic fibroblast (MEF). Seventeen genes with H3K27me3 loss and H3K4me3 gain showed marked upregulation, including p16Ink4a and Bmp2, a secreted factor for BMP/SMAD signal. Smad6, specific BMP/SMAD pathway inhibitor, was identified as the only one gene showing de novo H3K27 trimethylation with H3K4me3, resulting in strong repression. Ras-activated cells senesced with SMAD1/5/8 phosphorylation, and they escaped from senescence with decreased SMAD1/5/8 phosphorylation when introducing Smad6 or knocking-down Bmp2.
Publication Title
Activation of Bmp2-Smad1 signal and its regulation by coordinated alteration of H3K27 trimethylation in Ras-induced senescence.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
Description
To examine the role of SPS1 in mammals, we generated a Sps1 knockout mouse and found that systemic SPS1 deficiency was embryonic lethal. Embryos were clearly underdeveloped by E8.5 and virtually reabsorbed by E14.5. Removal of Sps1 specifically in hepatocytes using Albumin-cre preserved viability, but significantly affected expression of a large number of mRNAs involved in cancer, embryonic development and the glutathione system. Particularly notable was the extreme deficiency of glutaredoxin 1 (GLRX1) and glutathione-S-transferase omega 1. To assess these phenotypes at the cellular level, we targeted the removal of SPS1 in F9 cells, a mouse embryonal carcinoma cell line, which recapitulated changes in the glutathione system proteins. We further found that several malignant characteristics of SPS1-deficient F9 cells were reversed, suggesting that SPS1 has a role in supporting and/or sustaining cancer. In addition, the increased ROS levels observed in F9 SPS1/GLRX1 deficient cells were reversed and became more like those in F9 SPS1 sufficient cells by overexpressing mouse or human GLRX1. The results suggest that SPS1 is an essential mammalian enzyme with roles in regulating redox homeostasis and controlling cell growth.
Publication Title
Selenophosphate synthetase 1 is an essential protein with roles in regulation of redox homoeostasis in mammals.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
Description
The roles of histone demethylase KDM7 in gene expression were analyzed by gene expression profiling experiments with the mouse neuroblastoma cell line Neuro2A.
Publication Title
KDM7 is a dual demethylase for histone H3 Lys 9 and Lys 27 and functions in brain development.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 16 Downloadable Samples
Description
Treatment of DBA/2J mice with a combination of L-methionine and valproic acid significantly attenuated progressive hearing loss. We examined gene expression in the whole cochlea of the mice. This study was aimed to detect genes of which change in expression levels were associated with attenuation of progressive hearing loss in the mice.
Publication Title
Attenuation of progressive hearing loss in DBA/2J mice by reagents that affect epigenetic modifications is associated with up-regulation of the zinc importer Zip4.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 28 Downloadable Samples
Description
Sexual dimorphism of the behaviors or physiological functions in mammals is mainly due to the sex difference of the brain. The goal of this study is to identify genes mediating sexaul dimorphism of the brain.
Publication Title
Microarray analysis of perinatal-estrogen-induced changes in gene expression related to brain sexual differentiation in mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Description
To clarify how Foxp3 regulates its target genes, we performed co-immunoprecipitation experiments and found that Foxp3 physically bound to AML1/Runx1 (Ono, M. et al, Nature, 2007). In this series of study, we compared gene regulations by AML1, wild type Foxp3, and a Foxp3 mutant with defective binding to AML1.
Publication Title
Foxp3 controls regulatory T-cell function by interacting with AML1/Runx1.
Sample Metadata Fields
No sample metadata fields
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