Modulation of c-"os gene transcription by negative and positive cellular factors

Sassone–Corsi, Paolo; Verma, Inder M.

doi:10.1038/326507a0

Cited by 110 publications

(46 citation statements)

References 26 publications

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“…We have demonstrated that in asynchronously growing HeLa cells, induction of c-fos by both EGF Recent observations from in vivo competition experiments with transfected genes suggest that c-fos expression may be regulated by negatively acting factors as well as requiring a positive factor(s) (37). We have not found any evidence for a negatively acting factor from our mutational analysis; however, we would not have detected one if such a factor bound to the enhancer region and if our point mutations in the enhancer abolished binding of both the negatively and positively acting factors.…”

Section: Discussionmentioning

confidence: 99%

c-fos sequence necessary for basal expression and induction by epidermal growth factor, 12-O-tetradecanoyl phorbol-13-acetate and the calcium ionophore.

Fisch¹,

Prywes²,

Roeder³

1987

Mol. Cell. Biol.

270

181

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We have investigated the sequence requirements for induction of the human c-fos gene by epidermal growth factor (EGF), 12-0-tetradecanoyl phorbol-13-acetate (TPA), and the calcium ionophore A23187 by transfecting c-fos promoter mutants into HeLa and A431 cells. Induction by both EGF and TPA in HeLa cells required the presence of the c-fos enhancer located at -317 to -298 relative to the mRNA cap site. A23187, however, did not induce expression of the transfected gene, even though it strongly induced expression of the endogenous gene, suggesting that it has different requirements for induction than do EGF and TPA. We have also investigated the role of promoter sequences downstream of the enhancer in general expression and induction of c-fos. A sequence between -97 and -76, which includes an 8-base-pair perfect direct repeat, was needed for efficient general expression but not for induction of the gene. A factor in nuclear extracts that bound specifically to this sequence was detected by a gel mobility shift assay. A 7-base-pair sequence, located between -63 and -57 relative to the mRNA cap site and previously shown to be important for general expression of mouse c-fos, was also important for general expression of the human gene. In addition, this element was important for inducibility by EGF and TPA, since induction was significantly reduced when internal deletion mutants that retained the enhancer but lacked the -63 to -57 sequence element were analyzed in transfection assays.

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Section: Discussionmentioning

confidence: 99%

c-fos sequence necessary for basal expression and induction by epidermal growth factor, 12-O-tetradecanoyl phorbol-13-acetate and the calcium ionophore.

Fisch¹,

Prywes²,

Roeder³

1987

Mol. Cell. Biol.

270

181

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“…It is known that the c-fos oncogene group interacts with many stimulants and plays a role in cell growth and development (26). Generally, increased expressions of FOS in malignant tumors were also observed in fibroblasts when they were in stress.…”

Section: Discussionmentioning

confidence: 81%

Immune and inflammatory gene expressions are different in Behçet’s disease compared to those in Familial Mediterranean Fever

et al. 2017

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Objective: The immune classification of Behçet's disease (BD) is still controversial. In this study, we aimed to compare the immune/ inflammatory gene expressions in BD with those in familial Mediterranean fever (FMF), an autoinflammatory disorder with innate immune activation.Material and Methods: CD4+ T cells and CD14+ monocytes were isolated from the peripheral blood mononuclear cells of Behçet's disease patients (n=10), FMF (n=6) patients, and healthy controls (n=4) with microbeads, and then, the mRNA was isolated. The expressions of 440 genes associated with immune and inflammatory responses were studied with a focused DNA microarray using a chemiluminescent tagging system. Changes above 1.5-fold and below 0.8-fold were accepted to be significant. Results:In BD patients, in the CD4+ T-lymphocyte subset, interleukin 18 receptor accessory protein (1.7-fold), IL-7 receptor (1.9-fold), and prokineticin 2 (2.5-fold) were all increased compared to those in FMF patients, whereas chemokine (C-X3-C motif ) receptor-1 (CX3CR1) (0.7-fold) and endothelial cell growth factor-1 (0.6-fold) were decreased. In the CD14+ monocyte population, the V-fos FBJ murine osteosarcoma viral oncogene homolog (1.5-fold), Interleukin-8 (IL-8) (2.1-fold), and Tumor Necrosis Factor alpha (TNF-α) (1.8-fold) were all increased, whereas the chemokine (C-C motif ) ligand 5 (CCL5) (0.6-fold), C-C chemokine receptor type 7 (0.6-fold), and CX3CR1 (0.7-fold) were decreased, again when compared to those in FMF. Compared to healthy controls in the CD4+ T-lymphocyte population, in both BD and FMF patients, pro-platelet basic protein and CD27 had elevated expression. In BD and FMF patients, 24 and 19 genes, respectively, were downregulated, with 15 overlapping genes between both disorders. In the CD14+ monocytes population, chemokine (C-C motif ) receptor-1 (CCR1) was upregulated both in BD and FMF patients compared to that in the controls, whereas CCL5 was downregulated. Conclusion:Immune and inflammatory gene expressions seem to be variable in both the innate (CD14+) and adaptive (CD4+) immune responses in BD and FMF patients compared to those in controls, suggesting differences in immune regulation between the two disorders.

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“…Many examples of mammalian transcription units that contain cis-acting negative regulatory elements are now well documented. In particular, most of these genes are susceptible to induction by hormonal or environmental influences (12,31) or show very restricted patterns of tissue expression (17,25 genes. This mechanism would ensure that genes remain transcriptionally silent in the absence of the proper cellular signals or in inappropriate cell types.…”

Section: Discussionmentioning

confidence: 99%

“…interferon gene (12) and the c-fos gene (31), contain negative cis-acting transcriptional elements. Additionally, some cellular genes whose expression is regulated in a tissue-specific manner-for example, the rat insulin gene (25) and the immunoglobulin heavy-chain gene (17)-also contain cisacting negative elements.…”

mentioning

confidence: 99%

Negative regulation of transcription in vitro by a glucocorticoid response element is mediated by a trans-acting factor.

Langer¹,

Ostrowski²

1988

Mol. Cell. Biol.

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In vitro experiments with cell extracts prepared from a mouse mammary epithelial cell line demonstrated that a cis-acting glucocorticoid response element (GRE) of the mouse mammary tumor virus represses transcription from its homologous promoter. Competition transcription experiments, in which a molar excess of a restriction fragment that contains the GRE is added to the cell-free assay, revealed that a nuclear factor mediates in trans the negative regulation of mammary tumor virus transcription in vitro. Gel retention assays indicated that a factor in the extracts specifically recognizes the GRE. One unusual result of the gel retention studies was that heating the GRE probe to 65°C before addition to a binding assay increases the formation of the specific protein-DNA complex 20-fold. Exonuclease Ill footprinting demonstrated that the sequences recognized by the factor are identical for either untreated or heat-treated probe. The footprinting also demonstrated that this factor recognizes sequences that are distinct from those recognized by the glucocorticoid receptor. A synthetic oligonucleotide based on the sequences identified by the footprinting experiments repressed the activity of a heterologous enhancer-promoter in vivo, as assayed by transient expression assays.

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Modulation of c-"os gene transcription by negative and positive cellular factors

Cited by 110 publications

References 26 publications

c-fos sequence necessary for basal expression and induction by epidermal growth factor, 12-O-tetradecanoyl phorbol-13-acetate and the calcium ionophore.

c-fos sequence necessary for basal expression and induction by epidermal growth factor, 12-O-tetradecanoyl phorbol-13-acetate and the calcium ionophore.

Immune and inflammatory gene expressions are different in Behçet’s disease compared to those in Familial Mediterranean Fever

Negative regulation of transcription in vitro by a glucocorticoid response element is mediated by a trans-acting factor.

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