Involvement of a cis-Acting Element in the Suppression of Carbamoyl Phosphate Synthetase I Gene Expression in the Liver of Carnitine-Deficient Mice

Musa, Dewan Md. Abdullah Abu; Kobayashi, Keiko; Yasuda, Izumi; Iijima, Mikio; Christoffels, Vincent M.; Tomomura, Mineko; Horiuchi, Masahisa; Ohnishi, Tomokazu; Kajihara, Takeshi; Daikuhara, Yasushi; Lamers, W. H.; Saheki, Takeyori

doi:10.1006/mgme.1999.2905

Cited by 8 publications

(2 citation statements)

References 36 publications

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“…A possible mechanism involves the common transcription factor AP-1. Abdullah et al (28) showed binding of fatty acids to AP-1 (c-jun), which resulted in suppression of the expression of CPS1. Altered transcription can also occur in other genes that have a similar (putative) AP-1 enhancer site, such as ALB (29) and PCCA (30), and may be a generalized mechanism relevant to the development of fatty liver.…”

Section: Discussionmentioning

confidence: 99%

Identification of novel molecular candidates for fatty liver in the hyperlipidemic mouse model, HcB19

Greevenbroek

Vermeulen

Bruin

2004

Journal of Lipid Research

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The inbred HcB19 mouse strain expresses a truncated form of thioredoxin interacting protein and is phenotypically characterized by fatty liver and elevated plasma triglycerides and VLDL. Recently, these mice have been proposed as an animal model for familial combined hyperlipidemia. The aim of the present study was identification of hepatic proteins specifically associated with the presence of fatty liver. Eighteen differential proteins were detected in whole-liver homogenate from HcB19, or the parental strain C3H, using 2D electrophoresis, and 11 of those were successfully identified by mass spectrometry. Five of the identified differential proteins were mitochondrial, two peroxisomal, two cytosolic, and two secretory.

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Section: Discussionmentioning

confidence: 99%

Identification of novel molecular candidates for fatty liver in the hyperlipidemic mouse model, HcB19

Greevenbroek

Vermeulen

Bruin

2004

Journal of Lipid Research

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“…Transcription of CPS1 is activated by TATA-binding protein (TBP) while its proximal and distal enhancers contain binding sites for glucocorticoids and cAMP responsive factors including CCAAT-enhancer bind protein (C/EBP), activator protein-1 (AP-1), glucocorticoid receptor (GR) and cAMP response element binding (CREB). Sites for binding tissue specific factors including hepatic nuclear factor 3 (HNF-3) are also present [25], [30], [31]. Tissue specific expression of the OTC gene is induced in the intestine and liver by HNF-4, which binds in the promoter [13], [14], [32] while binding of both HNF-4 and C/EBP to the enhancer, induces high expression levels in the liver [12], [13], [14], [25], [33].…”

Section: Introductionmentioning

confidence: 99%

Transcriptional Regulation of N-Acetylglutamate Synthase

et al. 2012

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The urea cycle converts toxic ammonia to urea within the liver of mammals. At least 6 enzymes are required for ureagenesis, which correlates with dietary protein intake. The transcription of urea cycle genes is, at least in part, regulated by glucocorticoid and glucagon hormone signaling pathways. N-acetylglutamate synthase (NAGS) produces a unique cofactor, N-acetylglutamate (NAG), that is essential for the catalytic function of the first and rate-limiting enzyme of ureagenesis, carbamyl phosphate synthetase 1 (CPS1). However, despite the important role of NAGS in ammonia removal, little is known about the mechanisms of its regulation. We identified two regions of high conservation upstream of the translation start of the NAGS gene. Reporter assays confirmed that these regions represent promoter and enhancer and that the enhancer is tissue specific. Within the promoter, we identified multiple transcription start sites that differed between liver and small intestine. Several transcription factor binding motifs were conserved within the promoter and enhancer regions while a TATA-box motif was absent. DNA-protein pull-down assays and chromatin immunoprecipitation confirmed binding of Sp1 and CREB, but not C/EBP in the promoter and HNF-1 and NF-Y, but not SMAD3 or AP-2 in the enhancer. The functional importance of these motifs was demonstrated by decreased transcription of reporter constructs following mutagenesis of each motif. The presented data strongly suggest that Sp1, CREB, HNF-1, and NF-Y, that are known to be responsive to hormones and diet, regulate NAGS transcription. This provides molecular mechanism of regulation of ureagenesis in response to hormonal and dietary changes.

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Antagonizing Effect of AP-1 on Glucocorticoid Induction of Urea Cycle Enzymes: A Study of Hyperammonemia in Carnitine-Deficient, Juvenile Visceral Steatosis Mice

Saheki

Kobayashi

2000

Molecular Genetics and Metabolism

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Involvement of a cis-Acting Element in the Suppression of Carbamoyl Phosphate Synthetase I Gene Expression in the Liver of Carnitine-Deficient Mice

Cited by 8 publications

References 36 publications

Identification of novel molecular candidates for fatty liver in the hyperlipidemic mouse model, HcB19

Identification of novel molecular candidates for fatty liver in the hyperlipidemic mouse model, HcB19

Transcriptional Regulation of N-Acetylglutamate Synthase

Antagonizing Effect of AP-1 on Glucocorticoid Induction of Urea Cycle Enzymes: A Study of Hyperammonemia in Carnitine-Deficient, Juvenile Visceral Steatosis Mice

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