Independent and Cooperative Activation of Chromosomal c-fos Promoter by STAT3

Yang, Edward; Lerner, Lorena; Besser, Daniel; Darnell, E.

doi:10.1074/jbc.m213073200

Cited by 80 publications

(63 citation statements)

References 37 publications

(48 reference statements)

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“…4B). As already reported, whereas Socs3 induction was completely Stat3-dependent, c-Fos induction was only partially reduced in the absence of Stat3 (16,17). Remarkably, the putative Stat3-BSs associated to the Nfil3, Gadd45b, IL4ra, and Flt4 genes were all bound in vivo, the first 3 in an OSM-inducible way while Flt4 was bound constitutively (Fig.…”

Section: Validation Of Candidate Binding Sites By Measuring In Vivo Osupporting

confidence: 56%

Genome-wide discovery of functional transcription factor binding sites by comparative genomics: The case of Stat3

Vallania

Schiavone

Dewilde

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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The identification of direct targets of transcription factors is a key problem in the study of gene regulatory networks. However, the use of high throughput experimental methods, such as ChIP-chip and ChIP-sequencing, is limited by their high cost and strong dependence on cellular type and context. We developed a computational method for the genome-wide identification of functional transcription factor binding sites based on positional weight matrices, comparative genomics, and gene expression profiling. The method was applied to Stat3, a transcription factor playing crucial roles in inflammation, immunity and oncogenesis, and able to induce distinct subsets of target genes in different cell types or conditions. A newly generated positional weight matrix enabled us to assign affinity scores of high specificity, as measured by EMSA competition assays. Phylogenetic conservation with 7 vertebrate species was used to select the binding sites most likely to be functional. Validation was carried out on predicted sites within genes identified as differentially expressed in the presence or absence of Stat3 by microarray analysis. Twelve of the fourteen sites tested were bound by Stat3 in vivo, as assessed by Chromatin Immunoprecipitation, allowing us to identify 9 Stat3 transcriptional targets. Given its high validation rate, and the availability of large transcription factor-dependent gene expression datasets obtained under diverse experimental conditions, our approach appears to be a valid alternative to high-throughput experimental assays for the discovery of novel direct targets of transcription factors.chromatin immunoprecipitation ͉ phylogenetic footprint ͉ positional weight matrix ͉ Stat3 binding sites ͉ Stat3 target genes F unctional transcription factor binding sites (TFBSs) can be identified on a genomic scale either by computational approaches or through elaborated procedures such as chromatin immunoprecipitation followed by either genomic microchip hybridization (ChIP on Chip) or deep sequencing (ChIP and Sequencing) (1). These have the advantage of directly measuring the in vivo occupancy of genomic sites. By definition however, each experiment will only be able to identify sites bound under the specific conditions analyzed, i.e., separate experiments will have to be performed for each condition/tissue type of interest, and this will be particularly true for the many transcription factors (TF) that are known to induce distinct sets of genes in different tissues. Indeed, sets of TFBSs identified with these techniques in different conditions often show limited overlap. The predictions based on computational sequence analysis (2), however, are in principle independent of the cellular context. The ample collection of candidate BSs thus produced will then be available to identify transcriptional targets either as such or within lists of differentially expressed genes generated by microarray experiments, in many cases already available through public databases.The standard way to describe degenerate cis-regulator...

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Section: Validation Of Candidate Binding Sites By Measuring In Vivo Osupporting

confidence: 56%

Genome-wide discovery of functional transcription factor binding sites by comparative genomics: The case of Stat3

Vallania

Schiavone

Dewilde

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…For this, we used the c-fos, Bcl-x L , and VEGF promoters. The c-fos and Bcl-x L promoters are inducible by various cytokines and/or growth factors that act through the JAK-STAT pathway, and they contain well-characterized STAT binding sites (68,84). These promoters also contain GATA binding sites and are activated by GATA transcription factors (3,49).…”

Section: Resultsmentioning

confidence: 99%

Convergence of Protein Kinase C and JAK-STAT Signaling on Transcription Factor GATA-4

Wang

Paradis

Aries

et al. 2005

Molecular and Cellular Biology

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Angiotensin II (AII), a potent vasoactive hormone, acts on numerous organs via G-protein-coupled receptors and elicits cell-specific responses. At the level of the heart, AII stimulation alters gene transcription and leads to cardiomyocyte hypertrophy. Numerous intracellular signaling pathways are activated in this process; however, which of these directly link receptor activation to transcriptional regulation remains undefined. We used the atrial natriuretic factor (ANF) gene (NPPA) as a marker to elucidate the signaling cascades involved in AII transcriptional responses. We show that ANF transcription is activated directly by the AII type 1 receptor and precedes the development of myocyte hypertrophy. This response maps to STAT and GATA binding sites, and the two elements transcriptionally cooperate to mediate signaling through the JAK-STAT and protein kinase C (PKC)-GATA-4 pathways. PKC phosphorylation enhances GATA-4 DNA binding activity, and STAT-1 functionally and physically interacts with GATA-4 to synergistically activate AII and other growth factor-inducible promoters. Moreover, GATA factors are able to recruit STAT proteins to target promoters via GATA binding sites, which are sufficient to support synergy. Thus, STAT proteins can act as growth factor-inducible coactivators of tissue-specific transcription factors. Interactions between STAT and GATA proteins may provide a general paradigm for understanding cell specificity of cytokine and growth factor signaling.

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“…Thus, we examined whether Crif1 could influence the DNA binding of STAT3, which recognizes a conserved response element in the promoters of the genes encoding Socs3, c-Fos and Myc (Barre et al, 2003;Yang et al, 2003;Zhang et al, 2006). Crif1 þ /D and Crif1 À/D MEFs were stimulated with OSM for 10B30 min, and chromatin, prepared using a formaldehyde cross-linking protocol, was immunoprecipitated with an anti-STAT3 antibody.…”

Section: Figure 4 Defective Outgrowth Of Icm (A) and Massive Apoptosimentioning

confidence: 99%

“…Immunoprecipitation was performed with either the anti-STAT3 or the anti-HA antibody. The specific PCR primers were designed to contain putative STAT-binding sites, as determined by the MatInspector programme (Genomatix Software, Munchen, Germany), which spanned À166/À174 and À189/À197 in the SOCS3 promoter region (Zhang et al, 2006), À347/À355 in the c-fos promoter region (Yang et al, 2003), and À136/À146 in the c-myc promoter region (Barre et al, 2003). Real-time PCR was performed with a MyiQ single colour real-time PCR detection system (Bio-Rad) with iQ SYBR Green Supermix (Bio-Rad).…”

Section: Chip Analysismentioning

confidence: 99%

Crif1 is a novel transcriptional coactivator of STAT3

Kwon

Koo

Moon

et al. 2008

EMBO J

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Signal transducer and activator of transcription 3 (STAT3) is a transcriptional factor that performs a broad spectrum of biological functions in response to various stimuli. However, no specific coactivator that regulates the transcriptional activity of STAT3 has been identified. Here we report that CR6-interacting factor 1 (Crif1) is a specific transcriptional coactivator of STAT3, but not of STAT1 or STAT5a. Crif1 interacts with STAT3 and positively regulates its transcriptional activity. Crif1 À/À embryos were lethal around embryonic day 6.5, and manifested developmental arrest accompanied with defective proliferation and massive apoptosis. The expression of STAT3 target genes was markedly reduced in a Crif1 À/À blastocyst culture and in Oncostatin M-stimulated Crif1-deficient MEFs. Importantly, the key activities of constitutively active STAT3-C, such as transcription, DNA binding, and cellular transformation, were abolished in the Crif1-null MEFs, suggesting the essential role of Crif1 in the transcriptional activity of STAT3. Our results reveal that Crif1 is a novel and essential transcriptional coactivator of STAT3 that modulates its DNA binding ability, and shed light on the regulation of oncogenic STAT3.

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Independent and Cooperative Activation of Chromosomal c-fos Promoter by STAT3

Cited by 80 publications

References 37 publications

Genome-wide discovery of functional transcription factor binding sites by comparative genomics: The case of Stat3

Genome-wide discovery of functional transcription factor binding sites by comparative genomics: The case of Stat3

Convergence of Protein Kinase C and JAK-STAT Signaling on Transcription Factor GATA-4

Crif1 is a novel transcriptional coactivator of STAT3

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