Project description:The objective of this study was to dertemine GR binding patterns within wild type murine embryonic fibroblasts in comparison to embryonic fibroblasts derived from mice containing a null mutation for Klf15. This study utilized duplicate samples and the following conditions. Wild type cells treated with ethanol (pooled single sample secondary to low starting material); wild type cells treated with dexamethasone for 1 hour (2 samples); Klf15-/- cells treated with ethanol (2 samples); Klf15 -/- cells treated with dexamethasone (2 samples). Samples treated with ethanol served as controls.
Project description:By comparing the ChIPseq signal of REV_ERBa in control (Flox) and cardiomyocytic KLF15 knockout (cKO), we identified the KLF15 dependent REV-ERBa binding and repression in the heart. We further compared the differential binding sites to KLF15 binding site, using a FLAG tagged cardiomyocytic transgenic (cTG1) mice.
Project description:We characterize the KLF15 cistrome in vivo in skeletal muscle and find that the majority of KLF15 binding is localized to distal intergenic regions and associated with genes related to circadian rhythmicity and lipid metabolism. We identify critical interdependence between KLF15 and the nuclear receptor PPARδ in the regulation of lipid metabolic gene programs. We further demonstrate that KLF15 and PPARδ co-localize genome-wide, interact, and are dependent on one another to exert their transcriptional effects on target genes.
Project description:We used microarray analysis to identify differences in gene expression levels in heart following an 18h (overnight) fast in WT control and KLF15-null mice Heart tissue was isolated from 3-4 month old, 18h-fasted WT and KLF15-null male mice for RNA extraction and hydridization on Affymetrix microarrays
Project description:Circulating corticosteroids orchestrate stress adaptation, including inhibition of inflammation. While pathways governing corticosteroid biosynthesis and intracellular signaling are understood, less is known about mechanisms controlling plasma corticosteroid transport. Here, we show hepatocyte KLF15 (Kruppel-like factor 15) controls plasma corticosteroid transport and inflammatory responses through direct transcriptional activation of Serpina6, which encodes corticosteroid binding globulin (CBG). Klf15-deficient mice have profoundly low CBG, reduced plasma corticosteroid binding capacity, and heightened mortality during inflammatory stress. These defects are completely rescued by reconstituting CBG, supporting that KLF15 works primarily through CBG to control plasma corticosterone homeostasis. To understand transcriptional mechanisms, we generated the first KLF15 cistromes using newly engineered Klf153xFLAG mice. Unexpectedly, liver KLF15 is predominantly promoter-enriched, including Serpina6, where it binds a palindromic GC-rich motif, opens chromatin, and transactivates genes with minimal associated gene repression. Overall, we provide new mechanistic insight into KLF15 function and identify a hepatocyte-intrinsic transcriptional module that potently regulates systemic corticosteroid transport and inflammation.
Project description:We previously demonstrated that the transcription factor, KLF15, is a glucocorticoid-regulated gene that represses primary human airway smooth muscle (ASM) proliferation. Here, we show that KLF15 also represses ASM hypertrophy. To uncover the mechanistic basis for these effects, we integrated transcriptome data from KLF15 over-expression with genome-wide analysis of RNA Polymerase II (RNAPII) and glucocorticoid receptor (GR) occupancy (i.e. ChIP-seq). This led us to identify PLCD1 as both a KLF15-regulated gene and a repressor of ASM hypertrophy.
Project description:We used microarray analysis to identify differences in gene expression levels, in liver and in quadriceps skeletal muscle, between 18h (overnight) fasted WT control and Kruppel-like factor 15 (KLF15)-null mice. Experiment Overall Design: Liver and skeletal muscle (quadriceps) tissues were isolated from 4-5 month old, 18h-fasted WT and KLF15-null female mice for RNA extraction and hybridization on Affymetrix microarrays.
Project description:this dataset encompasses the cardiac KLF15 epigenomic changes elicited in 4-month-old mice with a single ZT0 prednisone (1mg/kg i.p.) injection
Project description:The glucocorticoid receptor (GR) regulates adaptive transcriptional programs that alter metabolism in response to stress. Network properties that allow GR to tune gene expression to match specific physiologic demands are poorly understood. We analyzed the transcriptional consequences of GR activation in murine lungs deficient for Klf15, a transcriptional regulator of amino acid metabolism that is induced by glucocorticoids and fasting Wild type and Klf15 KO mice were treated with dexamethsone or saline control for 4 and 8 hours.
Project description:this dataset encompasses the cardiac transcriptomic changes elicited in myocardial tissues of 4months-old mice at 4 hours after a single ZT0 prednisone (1mg/kg i.p.) injection, or vehicle, in cardiomyocyte-KLF15-WT versus cardiomyocyte-KLF15-KO conditions (inducible, tamoxifen-driven ablation right prior to drug pulse).
