Acetyl-CoA carboxylase beta gene is regulated by sterol regulatory element-binding protein-1 in liver.
Acetyl-CoA carboxylase (ACC) exists as two major isoforms originated from separate genes: ACCalpha (or ACC1) and ACCbeta (or ACC2). Previous data revealed that ACCbeta has two forms of mRNA with different 5'-untranslated regions derived by different usage of promoters, I and II, in human. In this study, we revealed that ACCbeta expression in liver is markedly stimulated by food intake at the transcriptional level. In the process of this induction in rat liver, promoter II plays the major role in regulating the expression of ACCbeta gene. The transient transfection with promoter II-luciferase reporters elucidated that the region from -93 to -38 nucleotides is important for the responsiveness to sterol regulatory element-binding protein-1 (SREBP-1), which is known to be the principle mediator for the stimulation of gene transcriptions by insulin and diet. The Sp1-binding site (-71 to -66) and neighboring two conserved SREs (-62 to -44) play a critical role in the stimulation of ACCbeta gene expression by SREBP-1. In vivo chromatin immunoprecipitation assay revealed that SREBP-1 directly bound to ACCbeta promoter II in liver, and its binding was regulated by the diet. This study provides evidence that ACCbeta expression in liver is regulated at the transcriptional level by the direct interaction of SREBP-1 with promoter II.
Oh
So-Young
SY
Department of Biochemistry and Molecular Biology, Institute of Genetic Science, Yonsei University College of Medicine, 134 Shinchondong Seodaemungu, Seoul 120-752, Korea.
Park
Sahng-Kyoo
SK
Kim
Jae-Woo
JW
Ahn
Yong-Ho
YH
Park
Sahng-Wook
SW
Kim
Kyung-Sup
KS
D000103:Acetyl-CoA Carboxylase / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000494:pharmacology*; D004032:Diet; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008099:Liver / Q000201:enzymology*; D008156:Luciferases / Q000235:genetics; D008297:Male; D009752:Nutritional Status; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020218:Response Elements; D016415:Sequence Alignment; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D014162:Transfection
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D004040:Dietary Carbohydrates; D007527:Isoenzymes; D012333:RNA, Messenger; C497387:SREBF1 protein, human; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D004247:DNA; D008156:Luciferases; D000103:Acetyl-CoA Carboxylase