Sp1 can displace GHF-1 from its distal binding site and stimulate transcription from the growth hormone gene promoter.

Lemaigre, Frédéric P.; Lafontaine, D A; Courtois, S J; Durviaux, S M; Rousseau, Guy

doi:10.1128/mcb.10.4.1811

Cited by 37 publications

(16 citation statements)

References 9 publications

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“…When the oligonucleotide containing the Sp1 binding sequence from the HGH promoter (20) was used as a probe with CEF extracts, it formed protein binding complexes in the same pattern as the Sp1 oligonucleotide corresponding to bp 618 -626 in the TTP intron (Fig. 6B).…”

Section: Nuclear Factor Binding To Intron Sequencesmentioning

confidence: 93%

“…For oligonucleotide Sp1, two complementary synthetic oligonucleotides (Life Technologies, Inc., Gaithersburg, MD) were annealed to form a doubled-stranded oligonucleotide corresponding to mouse intron sequence bp 617-629 (tcgacAGGGGCGGGGCGA), where underlined bases indicate the core sequences of the consensus Sp1-binding site (19). Double-stranded oligonucleotide HGHSp1 (tcgacTGTGTGGGAG-GAGCTTCTAG), which corresponds to the Sp1-binding site at Ϫ139 to Ϫ121 in the HGH promoter (20), was made the same way. A 5-base single-stranded tail (SalI site) was added to both ends of the two oligonucleotides for subcloning and fill-in labeling.…”

Section: Nuclear Extracts and Electrophoretic Mobility Shift Assaysmentioning

confidence: 99%

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Characteristics of the Intron Involvement in the Mitogen-induced Expression of Zfp-36

Lai

Thompson²,

Blackshear

1998

Journal of Biological Chemistry

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Zfp-36, the gene encoding the putative zinc finger protein tristetraprolin (TTP), is rapidly induced in fibroblasts by a variety of growth factors. Recent gene knockout experiments have shown that TTP-deficient mice developed arthritis, cachexia, and autoimmunity, all apparently mediated by an excess of tumor necrosis factor ␣. We recently showed that full serum inducibility of Zfp-36 requires elements in the promoter; in addition, removal of the single intron strikingly inhibited seruminduced TTP expression. We show here that replacement of the intron with unrelated sequences, or removal of 95% of the intron but retention of the splice sites, each resulted in the maintenance of approximately 45 and 19%, respectively, of full serum-induced expression. In addition, deletion of intron sequences base pairs 601-655 decreased the serum-induced expression of TTP by 65%. Sequence base pairs 618 -626 bound specifically to the transcription factor Sp1; mutation of this binding motif decreased TTP expression by 70%, suggesting that Sp1 binding to this motif contributes to serum induction of Zfp-36. We conclude that full serum-induced expression of Zfp-36 depends on the activation of conventional promoter elements as well as elements in the single intron, and that the presence per se of the intron in its natural location also contributes significantly to the regulated expression of this gene. Tristetraprolin (TTP)1 is a widely expressed protein containing two putative zinc fingers of the unusual CCCH class (1-5). It is the prototype of an enlarging group of proteins containing similar zinc fingers (6 -9). Although predominantly nuclear in quiescent fibroblasts, TTP is rapidly translocated from the nucleus to the cytoplasm by serum and other mitogens (10), an event that occurs concomitantly with stimulated serine phosphorylation (11). Although TTP has no proven function, disruption of its gene, Zfp-36, in mice leads to a complex syndrome that includes erosive arthritis, conjunctivitis, myeloid hyperplasia, cachexia, and autoimmunity (12). All aspects of the syndrome were prevented by pretreating the animals with monoclonal antibodies to tumor necrosis factor ␣ (TNF␣) (12). These data suggest that a potential function of TTP is to regulate the production of TNF␣ by certain cell types. They also indicate the possibility that defects in Zfp-36 might be involved in the pathogenesis of certain human conditions in which TNF␣ excess plays a role, such as rheumatoid arthritis and systemic lupus erythematosus.The transcription of Zfp-36 is rapidly and dramatically stimulated by a variety of growth factors and mitogens, but not by agents acting solely through increases in cAMP levels (1, 3, 4). Several transcription factor-binding sites have been identified in the Zfp-36 promoter that are each partially responsible for activating transcription in response to serum or insulin (13). In addition, we showed that the single intron of Zfp-36 also participates in the regulation of its transcription, since deletion of the intron results in a...

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Section: Nuclear Factor Binding To Intron Sequencesmentioning

confidence: 93%

Section: Nuclear Extracts and Electrophoretic Mobility Shift Assaysmentioning

confidence: 99%

Characteristics of the Intron Involvement in the Mitogen-induced Expression of Zfp-36

Lai

Thompson²,

Blackshear

1998

Journal of Biological Chemistry

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“…Two close binding sites in combination may form a composite element, which is a functional unit with new regulatory advantages due to the specific DNA-protein (63)(64)(65)(66)(67) and protein-protein interactions between trans-acting factors (7,(68)(69)(70)(71)(72)(73)(74). Structurally similar elements are present in quite different genes, which apparently implies that such regulatory modules are functionally significant.…”

Section: Introductionmentioning

confidence: 99%

“…The hierarchy of the regulatory modules and the functions of each level were considered earlier (55). (65,71,75,(81)(82)(83)(84)(85)(86) (16,17,19,(36)(37)(38)(39)(40)(41)(94)(95)(96)(97) and motifs responsible for multimerization (6,8,(97)(98) (67,80,84), lie adjacent to each other (84,85,91) or may be dozens of base pairs apart (66,80,82 Functional synergism between sites can be revealed by mutagenesis experiments, when one of the sites is to be intentionally destroyed. In this case, the level of activation, provided by the intact composite element, is much higher than the sum of the levels of activation provided by the interaction between either site alone and its corresponding factor (77,(84)(85)(86)(123)(124)(125)(126).…”

Section: Introductionmentioning

confidence: 99%

“…Another situation is when the repressor is displaced by the activator which wins the competition for binding to the same site on DNA (66,143,(144)(145)(146)(147)(148)(149)(150). Then the effects produced by the activator and repressor on transcription activity are opposing, which provides for a highly specific expression of the given gene in a definite cellular situation (in a particular cell type, at a stage of cell differentiation or ontogenesis etc.)…”

Section: Introductionmentioning

confidence: 99%

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