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Genome-Wide STAT5 binding sites in Kit225 leukemia cells

ABSTRACT: In order to systematically map STAT5 genomic binding sites and IL-2 mediated gene expression changes we mapped STAT5 binding sites using chip-on-ChIP in IL-2 dependent Kit225 cells that were either left un-stimulated or stimulated with IL-2 for 30 minutes. Using MAT analysis we identified 1581 STAT5 binding sites. IL2-stimulated Kit225 cells ChIPed with STAT5 antibodies vs. Input

ORGANISM(S): Homo sapiens

SUBMITTER: Zsuzsanna Nagy

PROVIDER: E-GEOD-40619 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Genome wide mapping reveals PDE4B as an IL-2 induced STAT5 target gene in activated human PBMCs and lymphoid cancer cells.

Nagy Zsuzsanna S ZS Ross Jeremy A JA Rodriguez Georgialina G Balint Balint L BL Szeles Lajos L Nagy Laszlo L Kirken Robert A RA

PloS one 20130225 2

IL-2 is the primary growth factor for promoting survival and proliferation of activated T cells that occurs following engagement of the Janus Kinase (JAK)1-3/and Signal Transducer and Activator of Transcription (STAT) 5 signaling pathway. STAT5 has two isoforms: STAT5A and STAT5B (commonly referred to as STAT5) which, in T cells, play redundant roles transcribing cell cycle and survival genes. As such, inhibition of STAT5 by a variety of mechanisms can rapidly induce apoptosis in certain lymphoi ...[more]

PMID: 23451206

Similar Datasets

IL-2 induced gene expression changes in Kit225 human leukemia cell lines

Project description:Identify IL-2 mediated genes in Kit225 cells. IL-2 withdrawn cells were treated with IL-2 or left untreated for 3 hours and then subjected to gene expression microarray analysis.

2013-03-21 | E-GEOD-40618 | biostudies-arrayexpress

Genome-wide mapping of IL-2 regulated target genes and IL-2 activated STAT5 binding sites in Kit225 human leukemia cells.

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-03-21 | E-GEOD-40624 | biostudies-arrayexpress

Genome-wide binding of STAT3 and STAT5 under Th17 conditions (ChIP-Seq)

Project description:Interleukin 2 (IL-2), a cytokine linked to human autoimmune diseases, limits IL-17 production. We show that deletion of Stat3 in T cells abrogates IL-17 production and attenuates autoimmunity associated with IL-2 deficiency. While STAT3 induces IL-17 and RORγt and inhibits Foxp3, IL-2 inhibited IL-17 independently of Foxp3 and RORγt. We found that STAT3 and STAT5 bound to multiple common sites across the Il17 genetic locus. The induction of STAT5 binding by IL-2 was associated with a reduction in STAT3 binding at these sites and the inhibition of associated active epigenetic marks. Titrating the relative activation of STAT3 and STAT5 modulated TH17 cell specification. Thus, the balance rather than the absolute magnitude of these signals determines the propensity of cells to make a key inflammatory cytokine. The genome-wide binding of STAT3 and STAT5 under Th17 conditions was investigated by CHIP-seq.

2011-02-09 | E-GEOD-26552 | biostudies-arrayexpress

Cytokine receptor modulation by interleukin-2 broadly regulates T helper cell lineage differentiation

Project description:T helper (Th) cells control host defense to pathogens. IL 12R expression is required for Th1, IL-4RM-NM-1 for Th2, and IL-6RM-NM-1/gp130 for Th17 differentiation to allow responsiveness to IL-12, IL-4, and IL-6, respectively. IL-2 via STAT5 controls Th2 differentiation by regulating the Th2 cytokine gene cluster and Il4ra expression. Here we show that IL-2 regulates Th1 differentiation, inducing STAT5-dependent IL-12RM-NM-22 and T-bet expression, with impaired human Th1 differentiation when IL-2 was blocked. Th1 differentiation was also impaired in mouse Il2-/- T cells but restored by IL-12RM-NM-22 expression. Consistent with IL-2M-bM-^@M-^Ys inhibition of Th17 differentiation, IL-2 decreased Il6ra and Il6st/gp130 expression, and Il6st augmented Th17 differentiation even when IL-2 was present. Thus, IL-2 influences T-cell differentiation by modulating cytokine receptor expression to help specify/maintain differentiated states. Genome-wide mapping of STAT1,STAT4,STAT5A,STAT5B binding to their target genes in Th1 or human CD4+ cells was conducted

2011-04-24 | E-GEOD-27158 | biostudies-arrayexpress

Roles of STAT3 and STAT5 in regulation of gene expression under Th17 differentiation

Project description:Interleukin 2 (IL-2), a cytokine linked to human autoimmune diseases, limits IL-17 production. We show that deletion of Stat3 in T cells abrogates IL-17 production and attenuates autoimmunity associated with IL-2 deficiency. While STAT3 induces IL-17 and ROR?t and inhibits Foxp3, IL-2 inhibited IL-17 independently of Foxp3 and ROR?t. We found that STAT3 and STAT5 bound to multiple common sites across the Il17 genetic locus. The induction of STAT5 binding by IL-2 was associated with a reduction in STAT3 binding at these sites and the inhibition of associated active epigenetic marks. Titrating the relative activation of STAT3 and STAT5 modulated TH17 cell specification. Thus, the balance rather than the absolute magnitude of these signals determines the propensity of cells to make a key inflammatory cytokine. The roles of STAT3 and STAT5 in regulation of gene expression under Th17 differentiation was investigated. Affymetrix Mouse Genome 430 2.0 Arrays were used to evaluate global gene expression.

2011-02-09 | E-GEOD-26551 | biostudies-arrayexpress

Genome-Wide STAT5 binding sites in Kit225 leukemia cells

Project description:In order to systematically map STAT5 genomic binding sites and IL-2 mediated gene expression changes we mapped STAT5 binding sites using chip-on-ChIP in IL-2 dependent Kit225 cells that were either left un-stimulated or stimulated with IL-2 for 30 minutes. Using MAT analysis we identified 1581 STAT5 binding sites.

2013-03-21 | GSE40619 | GEO

The gene encoding the hematopoietic stem cell regulator CCN3 (NOV) is under direct cytokine control through the transcription factors STAT5a/b.

Project description:Cytokines control the biology of hematopoietic stem and progenitor cells in part through the transcription factors STAT5a/b. CCN3/NOV has been reported as a positive regulator of hematopoietic stem and progenitor cells. We report microarray analyses of Lineage- Sca-1+ c-Kit+ (KSL) cells in the presence and absence of STAT5a/b. Expression of the ccn3 gene was induced over 100-fold in control, but not STAT5a/b-null cells, upon stimulation with a cocktail containing IL-3, IL-6, SCF, TPO and Flt3 ligand. Among the cytokines, IL-3 elevated ccn3 mRNA level in Lineage- c-Kit+ (KL) cells and 32D cells. ChIP assays using 32D cells revealed IL-3-induced binding of STAT5a/b to a GAS site in the ccn3 gene promoter. This is the first report to link two molecules with importance in the regulation of HSCs, CCN3 and STAT5a/b. We report that the regulation and expression of the ccn3 gene is directly controlled by IL-3 through the transcription factors STAT5a/b. Six Control and Six Stat5a/b-null KSL cells, including three biological replications, were unstimulated or stimulated with a cocktail containing IL-3, IL-6, SCF, TPO and FL.

2010-08-25 | E-GEOD-20684 | biostudies-arrayexpress

Genome-wide analyses reveal the extent of opportunistic STAT5 binding that does not yield transcriptional activation of neighboring genes.

Project description:Signal Transducers and Activators of Transcription (STAT) 5A/B regulate cytokine-inducible genes upon binding to GAS motifs. It is not known what percentage of genes with GAS motifs bind to and are regulated by STAT5. Moreover, it is not clear whether genome-wide STAT5 binding is modulated by its concentration. To clarify these issues we established genome-wide STAT5 binding upon growth hormone (GH) stimulation of wild type mouse embryonic fibroblasts (MEFs) and MEFs overexpressing STAT5A more than 20-fold. Upon GH stimulation 23,827 and 111,939 STAT5A binding sites were detected in wild type and STAT5A overexpressing MEFs, respectively. 13,278 and 71,561 peaks contained at least one GAS motif. 1,586 and 8,613 binding sites were located within 2.5 kbp of promoter sequences, respectively. Stringent filtering revealed 78 genes in which the promoter/upstream region (-10kbp to +0.5kbp) was recognized by STAT5 both in wt and STAT5 overexpressing MEFs and 347 genes that bound STAT5 only in overexpressing cells. Genome-wide expression analyses identified that the majority of STAT5-bound genes was not under GH control. Up to 40% of STAT5-bound genes were not expressed. For the first time we demonstrate the magnitude of opportunistic genomic STAT5 binding that does not translate into transcriptional activation of neighboring genes. Genome-wide mapping of STAT5 binding in MEF cells (WT, KO; Stat5-/- and overexpression; STAT5A-Stat5-/-) upon growth hormone induction

2012-01-12 | E-GEOD-34986 | biostudies-arrayexpress

Opposing actions of IL-2 and IL-21 on Th9 differentiation correlate with their differential regulation of BCL6 expression

Project description:Interleukin 9 (IL-9) is a γc-family cytokine that is highly produced by T-helper 9 (Th9) cells and regulates a range of immune responses, including allergic inflammation. Here we show that IL-2–JAK3–STAT5 signaling is required for Th9 differentiation, with critical STAT5 binding sites in the Il9 (the gene encoding IL-9) promoter. IL-2 also inhibited B cell lymphoma 6 (BCL6) expression, and over- expression of BCL6 impaired Th9 differentiation. In contrast to IL-2, IL-21 induced BCL6 and diminished IL-9 expression in wild-type but not Bcl6−/− cells, whereas Th9 differentiation was increased in Il21−/− or Il21r−/− T cells. Interestingly, BCL6 bound in proximity to many STAT5 and STAT6 binding sites, including at the Il9 promoter. Moreover, there was increased BCL6 and decreased STAT binding at this site in cells treated with blocking antibodies to IL-2 and the IL-2 receptor, suggesting a possible BCL6–STAT5 binding competition that influences IL-9 production. BCL6 binding was also increased when cells were Th9-differentiated in the presence of IL-21. Thus, our data reveal not only direct IL-2 effects via STAT5 at the Il9 gene, but also opposing actions of IL-2 and IL-21 on BCL6 expression, with increased BCL6 expression inhibiting IL-9 production. These data suggest a model in which increasing BCL6 expression decreases efficient Th9 differentiation, indicating possible distinctive approaches for controlling this process. Genome-wide transcription factors mapping and binding of STAT5B and STAT6 in mouse polarized Th9 cells treated with or without blocking antibodies to IL-2 (anti-IL-2). RNA-Seq is conducted in WT and Il2-/- mice.

2014-02-20 | E-GEOD-41317 | biostudies-arrayexpress

Active STAT5 in CD8 T cells imprints a T-Bet-dependent Tc-1 program with repressed IL-6/ TGFb1 signaling leading to enhanced anti-tumor responses

Project description:CD8 T cells (TCs) expressing active STAT5 (STAT5CA) transcription factors were found to be superior to un-manipulated counterparts in their long-term persistence, capacity to infiltrate a tumor, thrive in its microenvironment and induce its regression. STAT5CA induced sustained expression of genes controlling tissue homing, cytolytic granule composition, Tc-1-associated effector molecules (GranzymeB+/IFNg+/TNFa+/CCL3+ but IL-2-) and potential for secondary responses. Sustained expression of both T-Bet and Eomes transcription factors was correlated with STAT5 binding to their corresponding genes by ChIPSeq analyses. Additionally, STAT5CA-expressing CD8 TCs demonstrated reduced IL-6R/TGFbRII expression and dampened IL-6 and TGFb1 signaling. Altogether, concerted STAT5/T-Bet/Eomes regulation controls homing, recall responses and resistance to Tc-17 polarization in CD8 TCs. TCRP1A CD8 T lymphocytes were activated by their cognate P1A Ag. After 24h, an active form of Stat5 (STAT5CA) was introduced in activated cells. Culture was continued for another 48h to induce their differentiation in effector T cells. These activated T cells were injected in congeneic hosts and recovered 70 days later from hosts' spleen and lymph nodes: TCRP1A eTC-STAT5CA.

2013-09-13 | E-GEOD-41818 | biostudies-arrayexpress

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