A Fos-Jun element in the first intron of an α2u-globulin gene

Dijck, Patrick Van; Sassone–Corsi, Paolo; Auwerx, Johan; Verhoeven, Guido

doi:10.1007/bf00936441

Cited by 6 publications

(3 citation statements)

References 51 publications

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“…We have focused our initial analysis upon the first intron of the human gene, as it contains many sites that match the consensus sequences for binding by trans ‐acting factors. It is not uncommon for such intronic regions to contain important regulatory cis elements, including intronic AP‐1 sites 17–20. Although sequences 5′ to the start of transcription might be expected to participate in transcriptional regulation of SRace as well, this region apparently does not participate in responsiveness to proinflammatory stimuli.…”

Section: Discussionmentioning

confidence: 99%

Induction of Serine Racemase by Inflammatory Stimuli Is Dependent on AP‐1

Barger

2004

Annals of the New York Academy of Sciences

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Serine racemase (SRace) is an enzyme that catalyzes the conversion of L-serine to pyruvate or D-serine, an endogenous agonist for NMDA receptors. Our previous studies showed that inflammatory stimuli such as Abeta could elevate steady-state mRNA levels for SRace, perhaps leading to inappropriate glutamatergic stimulation under conditions of inflammation. We report here that a proinflammatory stimulus (lipopolysaccharide) elevated the activity of the human SRace promoter, as indicated by expression of a luciferase reporter system transfected into a microglial cell line. This effect corresponded to an elevation of SRace protein levels in microglia, as well. By contrast, dexamethasone inhibited the SRace promoter activity and led to an apparent suppression of SRace steady-state mRNA levels. A potential binding site for NFkappaB was explored, but this sequence played no significant role in SRace promoter activation. Instead, large deletions and site-directed mutagenesis indicated that a DNA element between -1382 and -1373 (relative to the start of translation) was responsible for the activation of the promoter by lipopolysaccharide. This region fits the consensus for an activator protein-1 binding site. Lipopolysaccharide induced an activity capable of binding this DNA element in electrophoretic mobility shift assays. Supershifts with antibodies against c-Fos and JunB identified these as the responsible proteins. An inhibitor of Jun N-terminal kinase blocked SRace promoter activation, further implicating activator protein-1. These data indicate that proinflammatory stimuli utilize a signal transduction pathway culminating in activator protein-1 activation to induce expression of serine racemase.

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Section: Discussionmentioning

confidence: 99%

Induction of Serine Racemase by Inflammatory Stimuli Is Dependent on AP‐1

Barger

2004

Annals of the New York Academy of Sciences

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“…It is therefore conceivable that all three binding sites constitute part of an intronic enhancer which controls both basal and induced transcription of the fra-1 gene. In this context, it is interesting that AP-1 regulatory sequences in an intron position have previously been shown to confer AP-1 responsiveness to the genes coding for cytokeratin 18 (41), nerve growth factor (21), and ␣ 2u -globulin (59).…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Activation of the fra-1 Gene by AP-1 Is Mediated by Regulatory Sequences in the First Intron

Bergers

Graninger

Braselmann

et al. 1995

Molecular and Cellular Biology

158

170

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Constitutive expression of c-Fos, FosB, Fra-1, or c-Jun in rat fibroblasts leads to up-regulation of the immediate-early gene fra-1. Using the posttranslational FosER induction system, we demonstrate that this AP-1-dependent stimulation of fra-1 expression is rapid, depends on a functional DNA-binding domain of FosER, and is a general phenomenon observed in different cell types. In vitro mutagenesis and functional analysis of the rat fra-1 gene in stably transfected Rat-1A-FosER fibroblasts indicated that basal and AP-1-regulated expression of the fra-1 gene depends on regulatory sequences in the first intron which comprise a consensus AP-1 site and two AP-1-like elements. We have also investigated the transactivating and transforming properties of the Fra-1 protein to address the significance of fra-1 up-regulation. The entire Fra-1 protein fused to the DNA-binding domain of Ga14 is shown to lack any transactivation function, and yet it possesses oncogenic potential, as overexpression of Fra-1 in established rat fibroblasts results in anchorage-independent growth in vitro and tumor development in athymic mice, fra-1 is therefore not only induced by members of the Fos family, but its gene product may also contribute to cellular transformation by these proteins. Together, these data identify fra-1 as a unique member of the fos gene family which is under positive control by AP-1 activity.

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“…1990), NGF (Hengerer et al . 1990), α 2u ‐globulin (vanDijck et al . 1993), and fra‐1 (Bergers et al .…”

Section: Discussionmentioning

confidence: 99%

The role of putative intragenic control elements in c‐fos regulation by calcium and growth factor signalling pathways

Lange

Bading

2001

Journal of Neurochemistry

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Sequences in the transcribed region of the c-fos gene have been suggested to control c-fos induction following exposure of cells to mitogens or stimuli that increase intracellular calcium concentrations. Using a mutational analysis we show that putative regulatory elements present in the ®rst intron of the human c-fos gene and the fos-intragenic-regulatoryelement (FIRE) are not required for c-fos regulation by growth factor and calcium signalling pathways in AtT20 and PC12 cells. Removal of the c-fos ®rst intron and the FIRE did not increase the basal level of c-fos mRNA and only moderately reduced the magnitude of calcium-induced transcription mediated by either the entire c-fos promoter or the cAMP response element (CRE). Intragenic mutations did not affect serum response element (SRE)-dependent gene expression induced by calcium signals but caused a superinduction of c-fos expression in nerve growth factor-stimulated PC12 cells. These results indicate that c-fos promoter elements, rather than intragenic sequences, are the principal targets of transcription-regulating signalling pathways. This suggests that CRE-and SRE-bound activators of transcription initiation may also enhance, in a signal-dependent manner, c-fos transcript elongation beyond promoter±proximal pause sites.

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A Fos-Jun element in the first intron of an α2u-globulin gene

Cited by 6 publications

References 51 publications

Induction of Serine Racemase by Inflammatory Stimuli Is Dependent on AP‐1

Induction of Serine Racemase by Inflammatory Stimuli Is Dependent on AP‐1

Transcriptional Activation of the fra-1 Gene by AP-1 Is Mediated by Regulatory Sequences in the First Intron

The role of putative intragenic control elements in c‐fos regulation by calcium and growth factor signalling pathways

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