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GSE53145
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The transcriptional repressor BLIMP1 is a master regulator of B and T cell differentiation. To examine the role of BLIMP1 in innate immunity we used a conditional knockout (CKO) of Blimp1 in myeloid cells and found that Blimp1 CKO mice were protected from lethal infection induced by Listeria monocytogenes. Transcriptome analysis of Blimp1 CKO macrophages identified the murine chemokine (C-C motif) ligand 8, CCL8 as a direct target of Blimp1-mediated transcriptional repression in these cells. BLIMP1-deficient macrophages expressed elevated levels of Ccl8 and consequently Blimp1 CKO mice had higher levels of circulating CCL8 resulting in increased neutrophils in the peripheral blood, promoting a more aggressive anti-bacterial response. Mice lacking the Ccl8 gene were more susceptible to L. monocytogenes infection than wild type mice. While CCL8 failed to recruit neutrophils directly, it was chemotactic for / T cells and CCL8-responsive / T cells were enriched for IL-17F. Finally, CCL8-mediated enhanced clearance of L. monocytogenes was dependent on / T cells. Collectively, these data reveal an important role for BLIMP1 in modulating host-defenses by suppressing expression of the chemokine CCL8.
Publication Title
The transcriptional repressor BLIMP1 curbs host defenses by suppressing expression of the chemokine CCL8.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
Ion Torrent Proton
Description
We previously reported a pathogenic de novo W342 mutation in the transcriptional corepressor CtBP1 in four independent patients with neurodevelopmental disabilities. Here, we report the clinical phenotypes of seven additional individuals with the same recurrent de novo CtBP1 mutation. Within this cohort we identified consistent CtBP1-related phenotypes of intellectual disability, ataxia, hypotonia and tooth enamel defects present in all patients. The W342 mutation in CtBP1 is located within a region implicated in a high affinity-binding cleft for CtBP-interacting proteins. Unbiased proteomic analysis demonstrated reduced interaction of several chromatin modifying factors with the CtBP1 W342 mutant. Genome-wide transcriptome analysis in human glioblastoma cells lines expressing -CtBP1 R342 (wt) or W342 mutation revealed changes in the expression profiles of genes controlling multiple cellular processes. Patient-derived dermal fibroblasts were found to be more sensitive to apoptosis during acute glucose deprivation compared to controls. Glucose deprivation strongly activated the BH3-only pro-apoptotic gene NOXA, suggesting a link between enhanced cell death and NOXA expression in patient fibroblasts. Our results suggest that context-dependent relief of transcriptional repression of the CtBP1 mutant W342 allele may contribute to deregulation of apoptosis in target tissues of patients leading to neurodevelopmental phenotypes. Overall design: Total RNA samples were isolated from 3 different cultures of HTB17 cells that overexpressed CtBP1 wt or the pathogenic mutant, W342 and analyzed by high- throughput RNA sequencing.
Publication Title
A pathogenic CtBP1 missense mutation causes altered cofactor binding and transcriptional activity.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Global analysis of gene expression in 10 day old brm-101 and syd-2 mutant seedlings compared to wild type Landsberg erecta seedlings.
Publication Title
Unique, shared, and redundant roles for the Arabidopsis SWI/SNF chromatin remodeling ATPases BRAHMA and SPLAYED.
Sample Metadata Fields
Age
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Whereas DNA methylation is essential for genomic imprinting, the importance of histone methylation in the allelic repression of imprinted genes is unclear. Imprinting control regions (ICRs), however, are consistently marked by histone H3 K9 methylation on their DNA-methylated allele. In the placenta, the paternal silencing along the Kcnq1 domain on distal chromosome 7 also correlates with the presence of H3-K9 methylation, but imprinted repression at these genes is maintained independently of DNA methylation. To explore which histone methyltransferase (HMT) could mediate the allelic H3-K9 methylation on distal chromosome 7, and at ICRs, we generated mouse conceptuses deficient for the SET-domain protein G9a. We find that in the embryo and placenta, the differential DNA methylation at ICRs and imprinted genes is maintained in the absence of G9a. Accordingly, in embryos, imprinted gene expression is unchanged at the domains analysed, in spite of a global loss of H3-K9 di-methylation (H3K9me2). In contrast, the placenta-specific imprinting of genes on distal chromosome 7 is lost in the absence of G9, and this correlates with a loss of H3K9me2 and H3K9me3. These findings provide the first in vivo evidence for the involvement of a SET domain protein in imprinting and highlight the importance of histone lysine methylation rather than DNA methylation in the maintenance of imprinting in the trophoblast lineage.
Publication Title
G9a histone methyltransferase contributes to imprinting in the mouse placenta.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 594 Downloadable Samples
- Affymetrix HT Mouse Genome 430A Array (htmg430a)
Description
We measured the genome-wide expression changes induced by 29 compounds targeting HDACs, DNMTs, histone lysine methyltransferases (HKMTs), and protein arginine methyltransferases (PRMTs) in pancreatic - and -cell lines.
Publication Title
Chromatin-targeting small molecules cause class-specific transcriptional changes in pancreatic endocrine cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
HO-1 inhibits preadipocyte proliferation and differentiation at the onset of obesity via ROS dependent activation of Akt2.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Excessive accumulation of white adipose tissue (WAT) is a hallmark of obesity. The expansion of WAT in obesity involves proliferation and differentiation of adipose precursors (APs), however, the underlying molecular mechanisms remain unclear. Here, we identify Heme Oxygenase-1 (HO-1) as selectively being upregulated in the AP fraction of WAT, upon high-fat diet (HFD) feeding. Specific conditional deletion of HO-1 in APs of Hmox1fl/fl-Pdgfra Cre mice enhanced HFD-dependent visceral AP proliferation and differentiation, upstream of Cebp and PPAR. Opposite effects on human preadipocyte proliferation and differentiation in vitro were observed following HO-1 overexpression. Mechanistically, HO-1 acts upstream of AKT2 via ROS thresholding in mitochondria. Deletion of HO-1 in APs is sufficient to lower blood glucose, insulin and free fatty acid levels as well as liver steatosis during obesity, an effect not seen when HO-1 was conditionally deleted at later stages of adipogenesis using AdipoQ-Cre. Together, our data identify HO-1 as a diet-induced regulator limiting visceral adipose tissue hyperplasia during obesity.
Publication Title
HO-1 inhibits preadipocyte proliferation and differentiation at the onset of obesity via ROS dependent activation of Akt2.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Excessive accumulation of white adipose tissue (WAT) is a hallmark of obesity. The expansion of WAT in obesity involves proliferation and differentiation of adipose precursors (APs), however, the underlying molecular mechanisms remain unclear. Here, we identify Heme Oxygenase-1 (HO-1) as selectively being upregulated in the AP fraction of WAT, upon high-fat diet (HFD) feeding. Specific conditional deletion of HO-1 in APs of Hmox1fl/fl-Pdgfra Cre mice enhanced HFD-dependent visceral AP proliferation and differentiation, upstream of Cebp and PPAR. Opposite effects on human preadipocyte proliferation and differentiation in vitro were observed following HO-1 overexpression. Mechanistically, HO-1 acts upstream of AKT2 via ROS thresholding in mitochondria. Deletion of HO-1 in APs is sufficient to lower blood glucose, insulin and free fatty acid levels as well as liver steatosis during obesity, an effect not seen when HO-1 was conditionally deleted at later stages of adipogenesis using AdipoQ-Cre. Together, our data identify HO-1 as a diet-induced regulator limiting visceral adipose tissue hyperplasia during obesity.
Publication Title
HO-1 inhibits preadipocyte proliferation and differentiation at the onset of obesity via ROS dependent activation of Akt2.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Altering TET dioxygenase levels within physiological range affects DNA methylation dynamics of HEK293 cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We compared TET1 and TET3 overexpressing cells to uninduced cells with endogenous levels of the respective transcript to determine global gene expression changes.
Publication Title
Altering TET dioxygenase levels within physiological range affects DNA methylation dynamics of HEK293 cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples