A nuclear factor 1 binding site mediates the transcriptional activation of a type I collagen promoter by transforming growth factor-β

Rossi, Pellegrino; Karsenty, Gérard; Roberts, Anita B.; Roche, Nanette S.; Sporn, Michael B.; Crombrugghe, Benoít de

doi:10.1016/s0092-8674(88)80033-3

Cited by 600 publications

(263 citation statements)

References 43 publications

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“…We found a CTF/NF-I binding site in a TGF-,-responsive region of the PAI-1 gene, similar to that reported by Rossi et al (42) for the a2(I)-collagen promoter, but in our system this site is adjacent to the binding sequence for USF and the integrity of both binding sites is necessary for the TGF-p response. It will be interesting to test whether another factor, besides CTF/NF-I, is also involved in the TGF-,B induction of the a2(I)-collagen gene.…”

Section: Plasmidssupporting

confidence: 91%

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Transforming growth factor beta 1-responsive element: closely associated binding sites for USF and CCAAT-binding transcription factor-nuclear factor I in the type 1 plasminogen activator inhibitor gene.

Riccio¹,

Pedone²,

Lund³

et al. 1992

Mol. Cell. Biol.

103

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Transforming growth factor 13 (TGF-3) is the name of a group of closely related polypeptides characterized by a multiplicity of effects, including regulation of extracellular proteolysis and turnover of the extracellular matrix. Its cellular mechanism of action is largely unknown. TGF-131 is a strong and fast inducer of type 1 plasminogen activator inhibitor gene transcription. We have identified a TGF-131-responsive element in the 5'-flanking region of the human type 1 plasminogen activator inhibitor gene and shown that it is functional both in its natural context and when fused to a heterologous nonresponsive promoter. Footprinting and gel retardation experiments showed that two different nuclear factors, present in extracts from both TGF-131-treated and nontreated cells, bind to adjacent sequences contained in the responsive unit. A palindromic sequence binds a trans-acting factor(s) of the CCAAT-binding transcription factor-nuclear factor I family. A partially overlapping dyad symmetry interacts with a second protein that much evidence indicates to be USF. USF is a transactivator belonging to the basic helix-loop-helix family of transcription factors. Mutations which abolish the binding of either CCAAT-binding transcription factor-nuclear factor I or USF result in reduction of transcriptional activation upon exposure to TGF-131, thus showing that both elements of the unit are necessary for the TGF-131 response. We discuss the possible relationship of these findings to the complexity of the TGF-13 action.Transforming growth factor I0 (TGF-3) is a general regulator of cellular activities with a multiplicity of effects in the normal organism. TGF-ps include a group of chemically closely related 25,000-Mr dimeric polypeptides, TGF-pl, , with largely identical effects. (Unless otherwise specified, "TGF-P3" will refer to TGF-fi1 heterodimers throughout the rest of the text.) TGF-,B can be synthesized by most cells of the organism and is stored in large quantities in blood platelets. It acts presumably in an autocrine and paracrine manner. Besides affecting cellular proliferation, TGF-3 influences the differentiation of several cell types; for instance, it inhibits myogenesis and adipogenesis and stimulates chondrogenesis. TGF-, regulates the turnover of the extracellular matrix. It stimulates production by fibroblasts of extracellular matrix components, such as type I, II, and III procollagen, fibronectin, and proteoglycans, and of cellular receptors for such proteins. TGF-1 inhibits production of enzymes catalyzing degradation of the extracellular matrix and stimulates production of inhibitors of such enzymes (22,27,31,41,47).It has previously been demonstrated that TGF-p induces type 1 inhibitor of plasminogen activators (PAI-1) in cultured human fibroblasts (24,26). PAI-1 is an important regulator of plasminogen activation and thus of extracellular proteolytic events, including fibrinolysis and degradation of the extracellular matrix (1, 6). The induction of PAI-1 protein by * Corresponding author. TGF-0 was la...

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Section: Plasmidssupporting

confidence: 91%

“…Concerning the cellular mechanism of action of TGF-,B effects unrelated to growth, Rossi et al (42) reported that a CTF/NF-I binding site alone confers TGF-P inducibility to the murine a2(I)-collagen gene. Kim et al (18,19) reported that TGF-1 autoinduction is mediated by the AP-1 complex.…”

Section: Plasmidsmentioning

confidence: 99%

Transforming growth factor beta 1-responsive element: closely associated binding sites for USF and CCAAT-binding transcription factor-nuclear factor I in the type 1 plasminogen activator inhibitor gene.

Riccio¹,

Pedone²,

Lund³

et al. 1992

Mol. Cell. Biol.

103

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“…The consensus site, for binding sites of both MPBF and NF-I, is well conserved within the region -206/-197 bp. The NF-I is a family of proteins generally regarded as ubiquitous transcriptional factors for various cellular and viral genes [45][46][47]. This proteins family is critical for the expression of liver-specific [48,49] and brain-specific genes [50], for activation of adipocyte-specific enhancer [51], and for epithelial cellspecific transcription [52].…”

Section: Identification Of Transcription Factor Binding Sitesmentioning

confidence: 99%

Polymorphisms of beta-lactoglobulin promoter region in three Sicilian goat breeds

et al. 2011

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Several beta-lactoglobulin (BLG) polymorphisms have been described within the proximal promoter region and coding region of the caprine gene, although no genetic variants affecting the protein amino acid composition and/or expression level have been characterized so far. Binding sites for several transcription factors (TFs) are present in the BLG promoter region. The aims of this work were to sequence the full-length promoter region of three Sicilian goat breeds in order to identify polymorphisms, analyze the identified haplotypes, search for differences between breeds for the presence of polymorphisms in this gene region, search for putative TFs binding sites, and check if polymorphisms lay within the identified TFs binding sites. The promoter region of BLG gene in Sicilian goat breeds showed high level of polymorphism due to the presence of 36 single nucleotide polymorphisms (SNPs). Association between polymorphic sites was computed within the whole sample analyzed and 18 haplotypes were inferred. Binding sites for three milk protein binding factors (MPBFs) and four nuclear factor-I (NF-I) were found within BLG promoter region based on the ovine sequence. The identification of some SNPs within TFs binding sites allowed hypothesizing the loss of TFs. Further studies are in progress to evaluate the effect of these mutations on binding affinity of TFs, the functional interaction of the TFs with the goat BLG promoter, and the relationship of the polymorphisms with BLG gene expression and milk production and composition.

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“…Thus, it appears that the effects of this statin are mediated by COL1A1 promoter elements previously recognized as participants in the up-regulation of collagen gene expression in systemic sclerosis (9,10). This possibility was explored further by the assessment of the binding activity of Sp1 and CBF, which are 2 transcriptional factors that play a crucial role in the regulation of COLlAl transcription, both under normal conditions and under the influence of TGF␤ (25,(27)(28)(29)(30)(31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of systemic sclerosis dermal fibroblast type I collagen production and gene expression by simvastatin

Louneva¹,

Huaman²,

Fertala³

et al. 2006

Arthritis & Rheumatism

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Objective. To examine whether statins are capable of modulating collagen gene expression in cultured systemic sclerosis dermal fibroblasts.Methods. Cultured dermal fibroblasts from 3 patients with diffuse systemic sclerosis of recent onset were treated with 5 M and 10 M of simvastatin for 3 or 4 days. Morphologic features, cytotoxicity, and type I collagen production and messenger RNA (mRNA) levels in the fibroblasts were examined. The effects of mevalonate, geranylgeranyl pyrophosphate (GGPP), and farnesyl pyrophosphate (FPP), which are lipids downstream from the hydroxymethylglutaryl-coenzyme A block, were also examined. Transient transfections with COL1A1 promoter-reporter constructs and electrophoretic gel mobility shift assays were utilized to examine COL1A1 transcription and Sp1 and CCAAT-box binding factor (CBF) binding.Results. Simvastatin did not cause morphologic changes or cytotoxicity in the fibroblasts, even after 4 days of treatment. Type I collagen production and mRNA levels showed a potent and dose-related inhibition following 3 and 4 days of treatment. The inhibition of collagen gene expression by simvastatin was completely reversed by mevalonate and GGPP, but not by FPP. The statin effects occurred at the transcriptional level and involved the proximal COL1A1 promoter region encompassing ؊174 bp. A significant reduction in Sp1 and CBF binding activity was also found in simvastatin-treated cells.

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A nuclear factor 1 binding site mediates the transcriptional activation of a type I collagen promoter by transforming growth factor-β

Cited by 600 publications

References 43 publications

Transforming growth factor beta 1-responsive element: closely associated binding sites for USF and CCAAT-binding transcription factor-nuclear factor I in the type 1 plasminogen activator inhibitor gene.

Transforming growth factor beta 1-responsive element: closely associated binding sites for USF and CCAAT-binding transcription factor-nuclear factor I in the type 1 plasminogen activator inhibitor gene.

Polymorphisms of beta-lactoglobulin promoter region in three Sicilian goat breeds

Inhibition of systemic sclerosis dermal fibroblast type I collagen production and gene expression by simvastatin

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