ACBP--a PPAR and SREBP modulated housekeeping gene.
The acyl-CoA binding protein (ACBP) is a 10 kD intracellular lipid binding protein that binds and transports acyl-CoA esters. The protein is expressed in most cell types at low levels; however, expression differs markedly between different cell types with expression being particularly high in e.g. cells with a high turnover of fatty acids. We show here that the relatively high basal promoter activity of the rat ACBP gene in fibroblasts and hepatoma cells relies on sequences between -331 to -182 and on the Sp1 and NF-Y sites at -172 and -143, respectively. The basal transcription is modulated by members of the PPAR and SREBP families. In adipocytes, PPARgamma is in part responsible for the induction during adipocyte differentiation, but other transcription factors appear to play a role as well. In hepatocytes, SREBP-1c is the main regulator of ACBP in response to changes in insulin levels during fasting/refeeding. PPARalpha counteracts this effect by stimulating ACBP expression during fasting. In addition, PPARalpha mediates the induction of ACBP expression in response to peroxisome proliferators. PPARalpha and PPARgamma do not require sequences upstream of -182 for transactivation; however, SREBP-1c requires the synergistic action of sequences in intron 1 for transactivation of the ACBP promoter.
Neess
Ditte
D
Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230, Odense M, Denmark.
Kiilerich
Pia
P
Sandberg
Maria B
MB
Helledie
Torben
T
Nielsen
Ronni
R
Mandrup
Susanne
S
D017667:Adipocytes / Q000378:metabolism / Q000502:physiology; D050156:Adipogenesis; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002478:Cells, Cultured; D026261:Diazepam Binding Inhibitor / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000378:metabolism; D007328:Insulin / Q000502:physiology; D007438:Introns; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D047493:PPAR alpha / Q000502:physiology*; D047495:PPAR gamma / Q000502:physiology*; D020025:Peroxisome Proliferators / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D051381:Rats; D051780:Sterol Regulatory Element Binding Protein 1 / Q000502:physiology*; D014158:Transcription, Genetic
D026261:Diazepam Binding Inhibitor; D007328:Insulin; D047493:PPAR alpha; D047495:PPAR gamma; D020025:Peroxisome Proliferators; D051780:Sterol Regulatory Element Binding Protein 1