Role of cyclic AMP in the control of cell-specific gene expression

Schmid, Wolfgang; Nitsch, Doris; Boshart, Michael; Schütz, Günther

doi:10.1016/1043-2760(93)90118-x

Cited by 7 publications

(4 citation statements)

References 45 publications

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“…HRUs are loci at which the activity of ubiquitous hormone-responsive factors depends on the nearby binding of other transcription factors. HRUs of genes expressed in liver generally require binding sites for members of one of the liver-enriched transcription factor families, like HNF3 or HNF4 and C/EBP (21,37,51,55,61,63). Our data show that the region between positions 320 and 400 of the 469-bp enhancer fragment (Fig.…”

Section: Discussionmentioning

confidence: 63%

Glucocorticoid Receptor, C/EBP, HNF3, and Protein Kinase A Coordinately Activate the Glucocorticoid Response Unit of the Carbamoylphosphate Synthetase I Gene

Christoffels

Grange

Kaestner

et al. 1998

Molecular and Cellular Biology

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A single far-upstream enhancer is sufficient to confer hepatocyte-specific, glucocorticoid-and cyclic AMPinducible periportal expression to the carbamoylphosphate synthetase I (CPS) gene. To identify the mechanism of hormone-dependent activation, the composition and function of the enhancer have been analyzed. DNase I protection and gel mobility shift assays revealed the presence of a cyclic AMP response element, a glucocorticoid response element (GRE), and several sites for the liver-enriched transcription factor families HNF3 and C/EBP. The in vivo relevance of the transcription factors interacting with the enhancer in the regulation of CPS expression in the liver was assessed by the analysis of knockout mice. A strong reduction of CPS mRNA levels was observed in glucocorticoid receptor-and C/EBP␣-deficient mice, whereas the CPS mRNA was normally expressed in C/EBP␤ knockout mice and in HNF3␣ and -␥ double-knockout mice. (The role of HNF␤ could not be assessed, because the corresponding knockout mice die at embryonic day 10). In hepatoma cells, most of the activity of the enhancer is contained within a 103-bp fragment, which depends for its activity on the simultaneous occupation of the GRE, HNF3, and C/EBP sites, thus meeting the requirement of a glucocorticoid response unit. In fibroblast-like CHO cells, on the other hand, the GRE in the CPS enhancer does not cooperate with the C/EBP and HNF3 elements in transactivation of the CPS promoter. In both hepatoma and CHO cells, stimulation of expression by cyclic AMP depends mainly on the integrity of the glucocorticoid pathway, demonstrating cross talk between this pathway and the cyclic AMP (protein kinase A) pathway.

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Section: Discussionmentioning

confidence: 63%

Glucocorticoid Receptor, C/EBP, HNF3, and Protein Kinase A Coordinately Activate the Glucocorticoid Response Unit of the Carbamoylphosphate Synthetase I Gene

Christoffels

Grange

Kaestner

et al. 1998

Molecular and Cellular Biology

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“…CREB actually belongs to a large multigene family of transcription factors, including the ATF family and API [6]. Although it is a ubiquitous factor it is also involved in tissue-specific gene expression [7]. It induces the expression of GHF-1/Pit-1, a pituitary-specific transcription factor [8], which activates growth hormone gene transcription.…”

Section: Introductionmentioning

confidence: 99%

“…Somatostatin gene expression is specific to pancreatic islet cells and its transcription is mediated by the co-operative activity of CREB and the pancreatic-specific factor Isl-1 [9]. Similarly in liver, activation of the tyrosine aminotransferase gene is dependent on synergy between the liver-specific factors, HNF3 and HNF4, and CREB [7,10].…”

Section: Introductionmentioning

confidence: 99%

Synergistic transcriptional activation of the thyrotropin receptor promoter by cyclic AMP-responsive-element-binding protein and thyroid transcription factor 1

Saiardi

Falasca

Civitareale

1995

Biochemical Journal

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In this study we have investigated the molecular mechanisms involved in hormonal induction of thyroid-specific transcription of the thyrotropin receptor (TSHr). A cyclic AMP-responsive element (CRE) has been characterized in the minimal TSHr promoter, and promoter activity shown to be also induced by thyroid transcription factor 1 (TTF-1). We here describe a cooperative effect between TTF-1 and CRE-binding protein on the TSHr promoter. Moreover we have identified a second TTF-1-binding site in the minimal promoter, which does not activate TSHr promoter activity but is required for the co-operative activation of the promoter. This report describes a new aspect of thyroid-specific gene expression, namely, how a generic extracellular signal can be interpreted in a thyroid-specific way.

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“…More than 15 years ago it was discovered that two classes of transcriptional regulators cooperate to ensure that the gluconeogenic program is activated only in the appropriate cell types, that is mainly in the hepatocytes of the liver (Schmid et al, 1993). The promoters and enhancers controlling the expression of the gluconeogenic genes contain binding sites for both liver-enriched transcription factors such as HNF4a and Foxa2 and also ubiquitously expressed transcription factors that mediate the activation of these genes in response to the changes in the hormonal milieu, such as the glucocorticoid receptor and the CREB family of transcription factors, which responds to changes in intracellular cAMP caused by increased glucagon and epinephrine.…”

mentioning

confidence: 99%