Transcriptional regulation of N-acetylglutamate synthase

PloS One
Sandra K HeibelLjubica Caldovic

Abstract

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 an...Continue Reading

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Citations

Oct 19, 2016·Biomarkers in Medicine·Nicolai J Wewer AlbrechtsenJens J Holst
Oct 17, 2018·Metabolic Syndrome and Related Disorders·Mia DemantFilip K Knop
Mar 17, 2020·American Journal of Physiology. Gastrointestinal and Liver Physiology·Katrine D GalsgaardJens J Holst
Apr 8, 2020·American Journal of Physiology. Endocrinology and Metabolism·Katrine D GalsgaardJens J Holst
Jan 24, 2019·Journal of Inherited Metabolic Disease·Leandro R Soria, Nicola Brunetti-Pierri
Jan 9, 2018·Mayo Clinic Proceedings·Sofie HædersdalTina Vilsbøll
Jul 3, 2021·International Journal of Molecular Sciences·Sung-Hwan ChoNam-Keun Kim

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Methods Mentioned

BETA
pull-down
immunoprecipitation
PCR
transfection
Assay
Rapid Amplification of cDNA Ends
pull down
DNA-pull down

Software Mentioned

PhastCons
BLAST
CLUSTALW
BLAST bl2seq
phyloP
element OVERrepresentation ( CLOVER )
CLOVER
Cis
UCSC genome browser
7900HT Sequence Detection System

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