Genome Wide Mapping of Foxo1 Binding-sites in Murine T Lymphocytes
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE60470 | GEO | 2014/08/19
SECONDARY ACCESSION(S): PRJNA258362
REPOSITORIES: GEO
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Project description:The Forkhead box O (Foxo) family of transcription factors has a critical role in controlling the development, differentiation, and function of T cells. However, the direct target genes of Foxo transcription factors in T cells have not been well characterized. In this study, we focused on mapping the genome wide Foxo1-binding sites in naïve CD4+ T cells, CD4+ T cells, and Foxp3+ regulatory T (Treg) cells. By using chromatin immunoprecipitation coupled with deep sequencing (ChIP-Seq), we identified Foxo1 binding sites that were shared among or specific to the three T cell populations. Here we describe the experiments, quality controls, as well as the deep sequencing data. Part of the data analysis has been published by Ouyang W et al. in Nature 2012 (1) and Kim MV et al. in Immunity 2013 (2), and the associated data set were uploaded to NCBI Gene Expression Omnibus. ChIP DNAs were prepared from T cells isolated from C57BL/6 mice using Foxo1 antibody and T cells isolated from Foxo1tag/tagbirA mice using Streptavin-coated beads. ChIP-seq libraries were prepared following a standard protocol.
2014-08-19 | E-GEOD-60470 | biostudies-arrayexpress
Project description:The mammalian FoxO transcription factors - FoxO1, FoxO3, FoxO4 - function in the nucleus to direct transcription of specific gene targets governing cellular survival, proliferation, metabolism, differentiation and oxidative defense. Activation of PI3K by extracellular growth factors leads to AKT-mediated phosphorylation of FoxO1, FoxO3 and FoxO4, resulting in their sequestration in the cytoplasm such that they are unable to regulate their gene targets. Our study identified FoxOs as novel tumor suppressors in kidney cancer (Gan et al, 2010, Cancer Cell). To understand the tumor suppression function of FoxOs in kidney cancer cells, we performed gene expression profiling in human kidney cancer cells upon FoxO1 or FoxO3 reactivation in order to identify the key transcriptomic alterations mediating FoxO tumor suppression function in kidney cancer cells. We generated RCC4 and UMRC2 cell lines (two human kidney cancer cells with low endogenous FoxO1 and FoxO3 expression) with stable expression of FoxO1(TA)ERT2 or FoxO3(TA)ERT2 construct, which expressed a fusion protein consisting of FoxO(TA) (containing three Ser/Thr AKT phosphorylation sites mutated to alanine) fused to the T2-modified estrogen receptor (ERT2) moiety. We documented that the FoxO(TA)ERT2 fusion protein sequestered FoxO(TA) in the cytoplasm and that 4OHT treatment resulted in rapid translocation of FoxO(TA)ERT2 into the nucleus. We also established stable cell lines with ERT2 expression as control cell lines. (For simplicity, ERT2, FoxO1(TA)ERT2 and FoxO3(TA)ERT2 cell lines will be referred to as EV (empty vector), FoxO1 and FoxO3, respectively, hereafter). We then conducted comparative transcriptome analysis (using the Human Genome U133 Plus 2.0 Array) of EV, FoxO1, or FoxO3-expressing RCC4 and UMRC2 cells at 12 hours with or without 100 nm 4OHT treatment (cultured in DMEM+10% FBS with puromycin selection). To enrich for more proximal actions of FoxO, we selected the 12 hour time point as time course studies revealed dramatic transcriptional changes of known FoxO targets (such as Cyclin D1), yet no discernable cellular phenotypes (apoptosis and cell cycle arrest). We generated 4 transcriptome datasets: FoxO1 RCC4, FoxO3 RCC4, FoxO1 UMRC2, and FoxO3 UMRC2 (by comparing transcriptome data with or without 4OHT treatment), and normalized these transcriptome data against 4OHT-treated EV cells, which show modest 4OHT-induced transcriptional changes.
2011-10-20 | E-GEOD-23926 | biostudies-arrayexpress
Project description:The mammalian FoxO transcription factors - FoxO1, FoxO3, FoxO4 - function in the nucleus to direct transcription of specific gene targets governing cellular survival, proliferation, metabolism, differentiation and oxidative defense. Activation of PI3K by extracellular growth factors leads to AKT-mediated phosphorylation of FoxO1, FoxO3 and FoxO4, resulting in their sequestration in the cytoplasm such that they are unable to regulate their gene targets. Our study identified FoxOs as novel tumor suppressors in kidney cancer (Gan et al, 2010, Cancer Cell). To understand the tumor suppression function of FoxOs in kidney cancer cells, we performed gene expression profiling in human kidney cancer cells upon FoxO1 or FoxO3 reactivation in order to identify the key transcriptomic alterations mediating FoxO tumor suppression function in kidney cancer cells.
2011-10-21 | GSE23926 | GEO
Project description:Identification of Foxos target genes in Treg cells. Foxo1and Foxo3 are transcription factors of Foxo family. CD4+Foxp3+ Treg cells isolated from wild-type and Foxo1/3-deficient mice were analyzed by global gene expression profiling. Results indicate Foxos regulate expression of a subset of Treg cell signature genes and genes in control of T cell homeostasis, signaling and metabolism. 2 sets wild-type and Foxo1/3-deficient CD4+Foxp3+ Treg cells
2010-09-13 | E-GEOD-21678 | biostudies-arrayexpress
Project description:The forkhead O transcription factors (FOXO) integrate a range of extracellular signals including growth factor signaling, inflammation, oxidative stress and nutrient availability, to substantially alter the program of gene expression and modulate cell survival, cell cycle progression, and many cell-type specific responses yet to be unraveled. Naive antigen-specific CD8+ T cells undergo a rapid expansion and arming of effector function within days of pathogen exposure, but in addition, by the peak of expansion, they form precursors to memory T cells capable of self-renewal and indefinite survival. We used microarrays to determine whether FOXO1 broadly affects effector and memory differentiation, and to what extent FOXO1 determines the program of memory T cell gene expression. To obtain an unbiased analysis of genes differentially expressed in antigen-specific Foxo1-/- CD8+ T cells responding to infection, we obtained RNA and performed Affymetrix microarray analysis from KLRG1low and KLRG1high FACS-sorted congenically-marked WT and Foxo1-/- P14 cells obtained from mixed transfers, eight days post-infection with LCMV-Armstrong. We carried out gene deletion in Rosa26Cre-ERT2 Foxo1f/f (Foxo1-/-) P14 mice just prior to adoptive transfer (Kerdiles et al., 2009), and transfer equal numbers of P14 cells from the spleens of KO (Foxo1-/- P14) and WT P14 mice. Day8 post infection
2013-04-13 | E-GEOD-46025 | biostudies-arrayexpress
Project description:A previous study has shown that PML-dependent recruitment of HIRA to ISG promoters contributes to the up-regulation of gene expression as a result of cytokine release in response to HSV infection (McFarlane et al., 2019). Although carried out in non-neuronal cells, this study and others (Ulbricht et al., 2012, Kim and Ahn, 2015, Scherer et al., 2016, Chen et al., 2015) suggest that PML itself may contribute to ISG upregulation, so to determine whether PML was indeed required for ISG stimulation in SCG neurons, we carried out RNA sequence analysis in IFNα-treated neurons depleted of PML.
2021-06-21 | GSE166738 | GEO
Project description:This data was generated by ENCODE. If you have questions about the data, contact the submitting laboratory directly (Yin Shen mailto:y7shen@ucsd.edu). If you have questions about the Genome Browser track associated with this data, contact ENCODE (mailto:genome@soe.ucsc.edu). This track shows a comprehensive survey of cis-regulatory elements in the mouse genome by using ChIP-seq (Robertson et al., 2007) to identify transcription factor binding sites and chromatin modification profiles in many mouse (C57Bl/6) tissues and primary cells, including bone marrow, cerebellum, cortex, heart, kidney, liver, lung, spleen, mouse embryonic fibroblast cells (MEFs) and embryonic stem (ES) cells. In specific, the Ren lab examined RNA polymerase II (PolII), co-activator protein p300, the insulator protein CTCF, and two chromatin modification marks H3K4me3 and H3K4me1 due to their demonstrated utilities in identifying promoters, enhancers and insulator elements (Barski et al., 2007; Blow et al., 2010; Heintzman et al., 2009; Kim et al., 2007; Kim et al., 2005a; Visel et al., 2009). Enrichment of H3K4me3 or PolII signals is a strong indicator of active promoter, while the presence of p300 or H3K4me1 outside of promoter regions has been used as a mark for enhancers. CTCF binding sites are considered as a mark for potential insulator elements. For each transcription factor or chromatin mark in each tissue, ChIP-seq was carried out with at least two biological replicates. Each experiment produced 20-30 million monoclonal, uniquely mapped tags. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf
2011-07-30 | GSE31039 | GEO
Project description:This data was generated by ENCODE. If you have questions about the data, contact the submitting laboratory directly (Yin Shen mailto:y7shen@ucsd.edu). If you have questions about the Genome Browser track associated with this data, contact ENCODE (mailto:genome@soe.ucsc.edu). This track shows a comprehensive survey of cis-regulatory elements in the mouse genome by using ChIP-seq (Robertson et al., 2007) to identify transcription factor binding sites and chromatin modification profiles in many mouse (C57Bl/6) tissues and primary cells, including bone marrow, cerebellum, cortex, heart, kidney, liver, lung, spleen, mouse embryonic fibroblast cells (MEFs) and embryonic stem (ES) cells. In specific, the Ren lab examined RNA polymerase II (PolII), co-activator protein p300, the insulator protein CTCF, and two chromatin modification marks, H3K4me3 and H3K4me1, due to their demonstrated utilities in identifying promoters, enhancers and insulator elements (Barski et al., 2007; Blow et al., 2010; Heintzman et al., 2009; Kim et al., 2007; Kim et al., 2005a; Visel et al., 2009). Enrichment of H3K4me3 or PolII signals is a strong indicator of an active promoter, while the presence of p300 or H3K4me1 outside of promoter regions has been used as a mark for enhancers. CTCF binding sites are considered as a mark for potential insulator elements. For each transcription factor or chromatin mark in each tissue, ChIP-seq was carried out with at least two biological replicates. Each experiment produced 20-30 million monoclonal, uniquely mapped tags. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf
2012-04-19 | GSE36027 | GEO
Project description:Investigation of whole genome gene expression level changes in neural progenitor cells derived from iPS cells generated from umbilical cord mesenchymal cells, compared to neural progenitor cells derived from iPS cells generated fromskin fibroblasts. Analyze the difference between neural progenitor cells derived from iPS cells generated from different origins. The method to induce reprogramming of somatic cells and human iPS cells for neural differentiation is described in Cai J, Li W, Su H, Qin D, Yang J, et al. (2010) Generation of human induced pluripotent stem cells from umbilical cord matrix and amniotic membrane mesenchymal cells. J Biol Chem 285: 11227-11234. and Kim DS, Lee JS, Leem JW, Huh YJ, Kim JY, et al. (2010) Robust enhancement of neural differentiation from human ES and iPS cells regardless of their innate difference in differentiation propensity. Stem Cell Rev 6: 270-281.
2013-05-06 | GSE46647 | GEO
Project description:Regulatory T (Treg) cells characterized by expression of the transcription factor forkhead box P3 (Foxp3) maintain immune homeostasis by suppressing self-destructive immune responses1-4. Foxp3 operates as a late acting differentiation factor controlling Treg cell homeostasis and function5, whereas the early Treg cell lineage commitment is regulated by the Akt kinase and the forkhead box O (Foxo) family of transcription factors6-10. However, whether Foxo proteins act beyond the Treg cell commitment stage to control Treg cell homeostasis and function remains largely unexplored. Here we show that Foxo1 is a pivotal regulator of Treg cell function. Treg cells express high amounts of Foxo1, and display reduced T-cell receptor-induced Akt activation, Foxo1 phosphorylation, and Foxo1 nuclear exclusion. Mice with Treg cell-specific deletion of Foxo1 develop a fatal inflammatory disorder similar in severity to Foxp3-deficient mice, but without the loss of Treg cells. Genome-wide analysis of Foxo1 binding sites reveals ~300 Foxo1-bound target genes, including the proinflammatory cytokine Ifng, that do not appear to be directly regulated by Foxp3. These findings demonstrate that the evolutionarily ancient Akt-Foxo1 signaling module controls a novel genetic program indispensable for Treg cell function. Treg cells were isolated from wild-type B6 mice or Foxo1tagBirA mice in which foxo1 is endogenously biotinylated. Foxo1 binding targets in Treg cells were identified by using Foxo1 antibody- and Streptavidin- ChIP-Seq approaches.
2012-09-07 | E-GEOD-40656 | biostudies-arrayexpress