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http://purl.uniprot.org/citations/18563384http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18563384http://www.w3.org/2000/01/rdf-schema#comment"

Aims/hypothesis

The glucose-6-phosphatase catalytic subunit (G6PC) plays a key role in hepatic glucose production by catalysing the final step in gluconeogenesis and glycogenolysis. Peroxisome proliferator activated receptor gamma coactivator-1alpha (PGC-1alpha) stimulates mouse G6pc-luciferase fusion gene expression through hepatocyte nuclear factor-4alpha (HNF-4alpha), which binds an element located between -76 and -64 in the promoter. The aim of this study was to compare the regulation of mouse G6pc and human G6PC gene expression by PGC-1alpha.

Methods

PGC-1alpha action was analysed by transient transfection and gel retardation assays.

Results

In H4IIE cells, PGC-1alpha alone failed to stimulate human G6PC-luciferase fusion gene expression even though the sequence of the -76 to -64 HNF-4alpha binding site is perfectly conserved in the human promoter. This difference could be explained, in part, by a 3 bp sequence variation between the mouse and human promoters. Introducing the human sequence into the mouse G6pc promoter reduced PGC-1alpha-stimulated fusion gene expression, whereas the inverse experiment, in which the mouse sequence was introduced into the human G6PC promoter, resulted in the generation of a G6PC-luciferase fusion gene that was now induced by PGC-1alpha. This critical 3 bp region is located immediately adjacent to a consensus nuclear hormone receptor half-site that is perfectly conserved between the mouse G6pc and human G6PC promoters. Gel retardation experiments revealed that this 3 bp region influences the affinity of HNF-4alpha binding to the half-site.

Conclusions/interpretation

These observations suggest that PGC-1alpha may be more important in the control of mouse G6pc than human G6PC gene expression."xsd:string
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http://purl.uniprot.org/citations/18563384http://purl.uniprot.org/core/author"Flemming B.P."xsd:string
http://purl.uniprot.org/citations/18563384http://purl.uniprot.org/core/author"O'Brien R.M."xsd:string
http://purl.uniprot.org/citations/18563384http://purl.uniprot.org/core/author"Oeser J.K."xsd:string
http://purl.uniprot.org/citations/18563384http://purl.uniprot.org/core/author"Schilling M.M."xsd:string
http://purl.uniprot.org/citations/18563384http://purl.uniprot.org/core/author"Allen S.R."xsd:string
http://purl.uniprot.org/citations/18563384http://purl.uniprot.org/core/author"Chandy J.K."xsd:string
http://purl.uniprot.org/citations/18563384http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18563384http://purl.uniprot.org/core/name"Diabetologia"xsd:string
http://purl.uniprot.org/citations/18563384http://purl.uniprot.org/core/pages"1505-1514"xsd:string
http://purl.uniprot.org/citations/18563384http://purl.uniprot.org/core/title"Sequence variation between the mouse and human glucose-6-phosphatase catalytic subunit gene promoters results in differential activation by peroxisome proliferator activated receptor gamma coactivator-1alpha."xsd:string
http://purl.uniprot.org/citations/18563384http://purl.uniprot.org/core/volume"51"xsd:string
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