Evidence map›Paper›PMID 9774647›Full record

ArticleMolecular and cellular biology1998

Glucocorticoid receptor, C/EBP, HNF3, and protein kinase A coordinately activate the glucocorticoid response unit of the carbamoylphosphate synthetase I gene.

V M Christoffels, T Grange, K H Kaestner, T J Cole, G J Darlington, C M Croniger, W H Lamers

Abstract read
In one paragraph

Article in Molecular and cellular biology, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
1.0field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 86 citations in OpenAlex.

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  7. CPS1: Looking at an ancient enzyme in a modern light.Molecular genetics and metabolism · 2020
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 6 institutions in 6 countries.

V M ChristoffelsDepartment of Anatomy and Embryology, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
T Grange
K H Kaestner
T J Cole
G J Darlington
C M Croniger
W H Lamers
University of Amsterdam · NLBaker Heart and Diabetes Institute · AUBaylor College of Medicine · USCase Western Reserve University · USCentre National de la Recherche Scientifique · FRMedical Genetics Center · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A single far-upstream enhancer is sufficient to confer hepatocyte-specific, glucocorticoid- and cyclic AMP-inducible 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/EBPalpha-deficient mice, whereas the CPS mRNA was normally expressed in C/EBPbeta knockout mice and in HNF3alpha and -gamma double-knockout mice. (The role of HNFbeta 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.

Indexed as

AnimalsBase SequenceCarbamoyl-Phosphate Synthase (Ammonia)CCAAT-Enhancer-Binding ProteinsCHO CellsCricetinaeCyclic AMPCyclic AMP-Dependent Protein KinasesDeoxyribonuclease IDNA-Binding ProteinsEnhancer Elements, GeneticGene Expression RegulationHepatocyte Nuclear Factor 3-betaIn Situ HybridizationLiverMiceCarbamoyl-Phosphate Synthase (Ammonia)CCAAT-Enhancer-Binding ProteinsCyclic AMPCyclic AMP-Dependent Protein KinasesDeoxyribonuclease IDNA-Binding ProteinsFoxa2 protein, mouseHepatocyte Nuclear Factor 3-betaNuclear ProteinsReceptors, GlucocorticoidRNA, MessengerTranscription Factors

Identifiers

PMID9774647
PMCPMC109217
OpenAlexW2108161900

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.