The transcription factor Peroxisome Proliferator-Activated Receptor (PPAR) is an important regulator of hepatic lipid metabolism. While PPAR is known to activate transcription of numerous genes, no comprehensive picture of PPAR binding to endogenous genes has yet been reported. To fill this gap, we performed ChIP-chip in combination with transcriptional profiling on HepG2 human hepatoma cells treated with the PPAR agonist GW7647. We found that GW7647 increased PPAR binding to 4220 binding regions. GW7647-induced binding regions showed a bias around the transcription start site and most contained a predicted PPAR binding motif. Several genes known to be regulated by PPAR, such as ACOX1, SULT2A1, ACADL, CD36, IGFBP1 and G0S2, showed GW7647-induced PPAR binding to their promoter. A GW7647-induced PPAR-binding region was also assigned to SREBP-targets HMGCS1, HMGCR, FDFT1, SC4MOL, and LPIN1, expression of which was induced by GW7647, suggesting cross-talk between PPAR and SREBP signaling. Our data furthermore demonstrate interaction between PPAR and STAT transcription factors in PPAR-mediated transcriptional repression, and suggest interaction between PPAR and TBP and C/EBP in PPAR-mediated transcriptional activation. Overall, our analysis leads to important new insights into the mechanisms and impact of transcriptional regulation by PPAR in human liver and highlight the importance of cross-talk with other transcription factors.
Profiling of promoter occupancy by PPARalpha in human hepatoma cells via ChIP-chip analysis.
Specimen part, Cell line, Treatment
View Samples[Gro-seq] Precursor B acute leukemia cells measured using global nuclear run-on sequencing [ChIP-Seq] The genome-wide occupancy of ser2 and ser5 phosphorylated RNA pol2 and H3K4me3 was measured in precursor B acute leukemia cells measured using chip-seq. Overall design: [Gro-seq] Nascent RNA expression profiles were generated at cells in various basal culture conditions. [ChIP-Seq] Performed from REH and Nalm6 cells cultured under basal culture conditions. Mnase digestion was used for DNA fragmentation. Antibodies against Ser2 and Ser5 phosphorylated RNA polymerase and H3K4me3 compared to input. ****************************** This study includes reanalysis of Samples in Series GSE39878 (GSM980645, GSM980644), GSE60454 (GSM1480326), and GSE41009 (GSM1006728, GSM100672). The processed data files for the reanalyses are linked to GSE67540 as supplementary files (see the GSE67540_README.txt file for additional information).
Transcription-coupled genetic instability marks acute lymphoblastic leukemia structural variation hotspots.
No sample metadata fields
View SamplesPpargc1a overexpression in heart tissue measured using RNA sequencing Overall design: RNA expression profiles were generated using RNA-seq from control (N=3) and Ppargc1a overexpressing (N=3) mice
Peroxisome proliferator-activated receptor-γ coactivator 1 α1 induces a cardiac excitation-contraction coupling phenotype without metabolic remodelling.
Specimen part, Treatment, Subject
View SamplesAround 20-25% of childhood acute lymphoblastic leukemias carry the TEL-AML1 (TA) fusion gene. It is a fusion of two central hematopoietic transcription factors, TEL (ETV6) and AML1 (RUNX1). Despite its prevalence, the exact genomic targets of TA have remained elusive. We evaluated gene loci and enhancers targeted by TA genome-wide in precursor B acute leukemia cells using global nuclear run-on sequencing (GRO-seq). Overall design: Nascent RNA expression profiles were generated with GRO-seq after TEL-AML1 expression in the Nalm6 pre-B-ALL cell line in four different time points (0, 4, 12 and 24 h). TEL-AML1-mut and luciferase induction cell lines were used as controls. Two replicates were included for all six samples.
Genome-wide repression of eRNA and target gene loci by the ETV6-RUNX1 fusion in acute leukemia.
No sample metadata fields
View SamplesStudy on gene expression in multifunctional protein 2 deficient mice. Liver samples of two days old mice in normal conditions are used. In total 8 arrays were hybridized corresponding to 4 KO mice and 4 WT mice Results: Cholesterol synthesis is induced and ppar alpha targets also differentially expressed between KO and WT.
Coordinate induction of PPAR alpha and SREBP2 in multifunctional protein 2 deficient mice.
No sample metadata fields
View SamplesGene expression profiling of in vitro differentiated murine Th cell subsets. Flow cytometrically sorted naive Th cells (CD4+ CD44- Foxp3-) were polyclonally stimulated in vitro for 3 days using 4 g/ml plate-bound antibody to CD3 (145-2C11) and 2 g/ml soluble antibody to CD28 (PV-1).
IL-27 and IL-12 oppose pro-inflammatory IL-23 in CD4+ T cells by inducing Blimp1.
Specimen part
View SamplesResistance of Saccharomyces cerevisiae to high furfural concentration is based on NADPH-dependent reduction by at least two oxireductases.
Resistance of Saccharomyces cerevisiae to high concentrations of furfural is based on NADPH-dependent reduction by at least two oxireductases.
No sample metadata fields
View SamplesLIN28 is an RNA-binding protein expressed in many developing tissues. It can block let-7 microRNA processing and help promote pluripotency. We observe LIN28 expression in the developing neural tube, colocalizing with SOX2, suggesting a role in neural development. To better understand its normal developmental function, we investigated LIN28 activity during neurogliogenesis in vitro where the succession of neuronal to glial cell fates occurs as it does in vivo. LIN28 expression was high in undifferentiated cells, and was down-regulated rapidly upon differentiation. Constitutive LIN28 expression caused a complete block of gliogenesis and an increase in neurogenesis. LIN28 expression was compatible with neuronal differentiation and did not increase proliferation. LIN28 caused significant changes in gene expression prior to any effect on let-7, notably on Igf2. Furthermore, a mutant LIN28 that permitted let-7 accumulation was still able to completely block gliogenesis. Thus, at least two biological activities of LIN28 are genetically separable and may involve distinct mechanisms. LIN28 can differentially promote and inhibit specific fates and does not function exclusively by blocking let-7 family miRNAs. Importantly, LIN28s role in cell fate succession in vertebrate cells is analogous to its activity as a developmental timing regulator in C. elegans.
LIN28 alters cell fate succession and acts independently of the let-7 microRNA during neurogliogenesis in vitro.
No sample metadata fields
View SamplesWe performed RNA-Seq and compared expression levels of genes of reactivated LCMV.GP66-77 specific CD4 T cells isolated from bone marrow (BM) and spleen of LCMV.GP61-80 primed C57BL/6 mice. Cells were isolated 3 days after antigenic re-challenge Overall design: C57BL/6 mice were primed at day 0 with LCMV.GP61-80-NP-MSA + poly(I:C) and immunized again at day 14 with LCMV.GP61-80 + poly(I:C). 60 days later, C57BL/6 mice were boosted with LCMV.GP61-80-NP-MSA + poly(I:C) and 3 days after the boost, LCMV specific CD4 T cells were isolated from BM and spleen
Nonfollicular reactivation of bone marrow resident memory CD4 T cells in immune clusters of the bone marrow.
Age, Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Melanoma-associated cancer-testis antigen 16 (CT16) regulates the expression of apoptotic and antiapoptotic genes and promotes cell survival.
Cell line, Treatment
View Samples