Endothelial cell activation and dysfunction underlie many vascular disorders, including atherosclerosis and inflammation. Here, we show that interleukin (IL)-4 markedly induced vascular cell adhesion molecule (VCAM)-1, both in cultured endothelial cells and in the intact endothelium in mice. Combined treatment with IL-4 and tumor necrosis factor (TNF)- alpha resulted in further, sustained induction of VCAM-1 expression. IL-4-mediated induction of VCAM-1 and secondary monocyte adhesion was predominantly regulated by the transcription factor, STAT6. Genome-wide survey of IL-4-mediated STAT6 binding from sequential chromatin-immunoprecipitation with deep-sequencing (ChIP-seq) in endothelial cells revealed regions of transient and sustained transcription factor binding. By combining DNA microarrays and ChIP-seq at the same time points, the majority of IL-4-responsive genes were shown to be STAT6-dependent and associated with direct STAT6 binding to their promoter. IL-4-mediated stable binding of STAT6 led to sustained target gene expression. Moreover, our strategy led to the identification of a novel functionally important STAT6 binding site within -16 kb upstream of the VCAM-1 gene. Taken together, these findings support a critical role for STAT6 in mediating IL-4 signal transduction in endothelial cells. Identification of a novel IL-4-mediated VCAM-1 enhancer may provide a foundation for targeted therapy in vascular disease (ChIP-seq data not submitted to GEO).
Genome-wide approaches reveal functional interleukin-4-inducible STAT6 binding to the vascular cell adhesion molecule 1 promoter.
Treatment
View Sampleswe performed genome-wide expression analyses for investigating novel genetic environmental changes.
Effect of adiponectin on kidney crystal formation in metabolic syndrome model mice via inhibition of inflammation and apoptosis.
Specimen part, Treatment
View SamplesAGRP neurons are a hypothalamic population that senses physiological energy deficit and consequently increases appetite. Molecular and cellular processes for energy-sensing and elevated neuronal output are critical for understanding the central nervous system response to energy deficit states, such as during weight-loss. Cell type-specific transcriptomics can be used to identify pathways that counteract weight-loss but, in adult mice, this has been limited by technical challenges. We report high-quality gene expression profiles of AGRP neurons under well-fed and energy deficit states. For comparison, we also analyzed POMC neurons, an intermingled population that suppresses appetite. This data newly identifies cell type-selective involvement of signaling pathways, ion channels, neuropeptides, and G-protein coupled receptors. Combined with methods to validate and manipulate these pathways, this resource greatly expands molecular insight into neuronal regulation of body weight, and may be useful for devising therapeutic strategies for obesity and eating disorders. Overall design: Examination of 2 different neuronal cell types under 2 conditions.
Cell type-specific transcriptomics of hypothalamic energy-sensing neuron responses to weight-loss.
No sample metadata fields
View SamplesAnalysis of mammary glands from tet-inducible (rtTA) transgenic mice expressing cyclin D1 (Ccnd1). MMTV-rtTA transgenic mice (MMTV-Mouse Mammary Tumor Virus promoter) were cross-mated to cyclin D1 transgenic mice under the control of the tet operon. 8-week-old tetracycline-inducible cyclin D1/rtTA bi-transgenic pregnant female mice (12 days postcoitus) were treated with doxycycline through drinking water supplementation at a final concentration of 2 mg/ml. Control mice were rtTA transgenics alone and were treated in the same manner. After 7 days of doxycycline treatment, the mice were sacrificed and mammary glands taken for RNA isolation. Results provide insight into the in vivo gene expression pattern regulated by cyclin D1 through acute induction.
ChIP sequencing of cyclin D1 reveals a transcriptional role in chromosomal instability in mice.
Specimen part
View Samplesaffy_ccr_maize - affy_ccr_maize - Cinnamoyl-CoA reductase (CCR) catalyzes a key step in monolignol biosynthesis. We show that downregulation of CCR in maize was associated with lower lignin content and a strong decrease in H units. Concomitantly, these cell wall modifications were associated with higher digestibility. On another hand, immunocytochemistry indicated a modification of lignification pattern and cellulose content. Transcript profiling was used as comprehensive phenotyping tools to investigate how CCR downregulation impacted metabolism and the biosynthesis of other cell wall polymers. -2 wild type and 2 CCR mutants were compared. Plants were grown in greenhouse condition and harvested at 7-8 leaf stages.
Characterization of a cinnamoyl-CoA reductase 1 (CCR1) mutant in maize: effects on lignification, fibre development, and global gene expression.
No sample metadata fields
View Samples