Identification of a liver-specific cAMP response element in the human argininosuccinate synthetase gene.
Argininosuccinate synthetase (ASS), a key enzyme in the urea cycle, participates in many metabolic processes including arginine biosynthesis and the citrulline-nitric oxide (NO) cycle. Factors like diets, hormones and pro-inflammatory stimuli are known to regulate ASS gene expression primarily at the transcription level. However, little is known about the cis-elements for transcriptional regulation of the ASS gene. In this study, we employed DNase I hypersensitive sites mapping to identify potential regulatory sites of the gene and revealed a site located at 10 kb upstream of the transcription start site which is responsible for liver-specific cAMP induction. Furthermore, a cAMP response element (CRE) highly conserved among mammals was identified and was experimentally verified. Our results show that liver-specific enhancement of ASS gene expression is mediated in part by the cAMP signaling pathway through a distal CRE site.
Guei
Tai-Ru
TR
Faculty of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan.
Liu
Mei-Chun
MC
Yang
Chun-Ping
CP
Su
Tsung-Sheng
TS
D001124:Argininosuccinate Synthase / Q000235:genetics*; D001483:Base Sequence; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000737:chemistry; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008099:Liver / Q000201:enzymology*; D020161:Physical Chromosome Mapping; D020218:Response Elements; D017422:Sequence Analysis, DNA
D017362:Cyclic AMP Response Element-Binding Protein; D004247:DNA; D003850:Deoxyribonuclease I; D001124:Argininosuccinate Synthase