Acetyl-CoA Carboxylase β Gene Is Regulated by Sterol Regulatory Element-binding Protein-1 in Liver

Abstract

Acetyl-CoA carboxylase (ACC) exists as two major isoforms originated from separate genes: ACCα (or ACC1) and ACCβ (or ACC2). Previous data revealed that ACCβ 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 ACCβ 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 ACCβ 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 ACCβ gene expression by SREBP-1. In vivo chromatin immunoprecipitation assay revealed that SREBP-1 directly bound to ACCβ promoter II in liver, and its binding was regulated by the diet. This study provides evidence that ACCβ expression in liver is regulated at the transcriptional level by the direct interaction of SREBP-1 with promoter II. Acetyl-CoA carboxylase (ACC) exists as two major isoforms originated from separate genes: ACCα (or ACC1) and ACCβ (or ACC2). Previous data revealed that ACCβ 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 ACCβ 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 ACCβ 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 ACCβ gene expression by SREBP-1. In vivo chromatin immunoprecipitation assay revealed that SREBP-1 directly bound to ACCβ promoter II in liver, and its binding was regulated by the diet. This study provides evidence that ACCβ expression in liver is regulated at the transcriptional level by the direct interaction of SREBP-1 with promoter II. Acetyl-CoA carboxylase (ACC) 1The abbreviations used are: ACC, acetyl-CoA carboxylase; SREBP, sterol regulatory element-binding protein; EMSA, electrophoretic mobility shift assay; ChIP, chromatin immunoprecipitation assay; DMEM, Dulbecco's modified Eagle's medium; MEM, minimal essential medium; MOPS, 4-morpholinepropanesulfonic acid. catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, which is served not only as the substrate for fatty acid biosynthesis but also as a signal molecule for metabolic control of fatty acid β-oxidation in skeletal muscle and insulin secretion in pancreatic β cells (1Kim K.H. Annu. Rev. Nutr. 1997; 17: 77-99Crossref PubMed Scopus (314) Google Scholar). Two isoforms of ACC have been identified (ACCα and ACCβ). These two isoforms are encoded by the separate genes and display distinct tissue distribution. The α isoform of ACC (also called ACC1, 265 kDa) is mainly distributed in liver and adipose tissue, where lipogenesis is active. In contrast, the β isoform of ACC (also called as ACC2, 275 kDa) is the predominant carboxylase in skeletal muscle and heart, where fatty acid β-oxidation serves as the main energy source (2Zhang S. Kim K.H. Biochem. Biophys. Res. Commun. 1996; 229: 701-705Crossref PubMed Scopus (15) Google Scholar). ACCβ shows considerable homology to ACCα except the additional NH2-terminal portion, comprised of about 200 amino acids, which is known to direct ACCβ to the outer membrane of mitochondria (3Ha J. Lee J.K. Kim K.S. Witters L.A. Kim K.H. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 11466-11470Crossref PubMed Scopus (132) Google Scholar, 4Abu-Elheiga L. Brinkley W.R. Zhong L. Chirala S.S. Woldegiorgis G. Wakil S.J. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 1444-1449Crossref PubMed Scopus (329) Google Scholar). The level of malonyl-CoA generated by ACCβ around mitochondria functions as the important factor in regulating mitochondrial fatty acid β-oxidation through inhibition of carnitine palmitoyl-CoA transferase I. The activities of ACCβ in skeletal muscle are mainly regulated by phosphorylation and dephosphorylation but not by changes of enzyme contents (5Dyck J.R. Kudo N. Barr A.J. Davies S.P. Hardie D.G. Lopaschuk G.D. Eur. J. Biochem. 1999; 262: 184-190Crossref PubMed Scopus (137) Google Scholar, 6Boone A.N. Rodrigues B. Brownsey R.W. Biochem. J. 1999; 341: 347-354Crossref PubMed Scopus (44) Google Scholar, 7Minokoshi Y. Kim Y.B. Peroni O.D. Fryer L.G. Muller C. Carling D. Kahn B.B. Nature. 2002; 415: 339-343Crossref PubMed Scopus (1691) Google Scholar, 8Winder W.W. Hardie D.G. Am. J. Physiol. 1996; 270: E299-E304Crossref PubMed Google Scholar). For example, sympathetic nerve stimulation or exercise increases the phosphorylation of ACCβ, resulting in the inhibition of ACCβ activities and the increase of fatty acid oxidation (7Minokoshi Y. Kim Y.B. Peroni O.D. Fryer L.G. Muller C. Carling D. Kahn B.B. Nature. 2002; 415: 339-343Crossref PubMed Scopus (1691) Google Scholar, 8Winder W.W. Hardie D.G. Am. J. Physiol. 1996; 270: E299-E304Crossref PubMed Google Scholar, 9Rasmussen B.B. Winder W.W. J. Appl. Physiol. 1997; 83: 1104-1109Crossref PubMed Scopus (130) Google Scholar, 10Dean D. Daugaard J.R. Young M.E. Saha A. Vavvas D. Asp S. Kiens B. Kim K.H. Witters L. Richter E.A. Ruderman N. Diabetes. 2000; 49: 1295-1300Crossref PubMed Scopus (102) Google Scholar, 11Vavvas D. Apazidis A. Saha A.K. Gamble J. Patel A. Kemp B.E. Witters L.A. Ruderman N.B. J. Biol. Chem. 1997; 272: 13255-13261Abstract Full Text Full Text PDF PubMed Scopus (348) Google Scholar). ACCβ is also expressed in liver and HepG2 cells (4Abu-Elheiga L. Brinkley W.R. Zhong L. Chirala S.S. Woldegiorgis G. Wakil S.J. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 1444-1449Crossref PubMed Scopus (329) Google Scholar, 12Abu-Elheiga L. Almarza-Ortega D.B. Baldini A. Wakil S.J. J. Biol. Chem. 1997; 272: 10669-10677Abstract Full Text Full Text PDF PubMed Scopus (201) Google Scholar). Oxidation of fatty acid also occurs actively in liver, but its regulation is different from that in skeletal muscle. In liver, fatty acid oxidation is increased during the fasting period and is almost blocked by food intake, whereas in skeletal muscle, nutritional status does not change the rate of oxidations of fatty acids significantly. Interestingly, animals lacking ACCβ showed marked increase in blood ketone bodies by overnight fasting compared with wild type animals (13Abu-Elheiga L. Matzuk M.M. Abo-Hashema K.A. Wakil S.J. Science. 2001; 291: 2613-2616Crossref PubMed Scopus (752) Google Scholar). These facts suggest the possibility that ACCβ might also control fatty acid oxidation in liver and the regulation of its activities might be different in liver and muscle. Most of the lipogenic enzymes, including ACCα, fatty acid synthase, stearoyl-CoA desaturase-1, and ATP citrate-lyase, are regulated by dietary regimen and insulin at the transcription level in liver. These regulations are known to be mediated by SREBP-1, which is a member of the basic helix-loop-helix/leucine zipper family of transcription factors (14Tabor D.E. Kim J.B. Spiegelman B.M. Edwards P.A. J. Biol. Chem. 1999; 274: 20603-20610Abstract Full Text Full Text PDF PubMed Scopus (199) Google Scholar, 15Magana M.M. Lin S.S. Dooley K.A. Osborne T.F. J. Lipid Res. 1997; 38: 1630-1638Abstract Full Text PDF PubMed Google Scholar, 16Bennett M.K. Lopez J.M. Sanchez H.B. Osborne T.F. J. Biol. Chem. 1995; 270: 25578-25583Abstract Full Text Full Text PDF PubMed Scopus (334) Google Scholar, 17Moon Y.A. Lee J.J. Park S.W. Ahn Y.H. Kim K.S. J. Biol. Chem. 2000; 275: 30280-30286Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar, 18Andreolas C. da Silva Xavier G. Diraison F. Zhao C. Varadi A. Lopez-Casillas F. Ferre P. Foufelle F. Rutter G.A. Diabetes. 2002; 51: 2536-2545Crossref PubMed Scopus (55) Google Scholar). SREBP-1 has been identified as two isoforms (SREBP-1a and -1c) derived from a single gene through the use of alternative transcription start sites and splicing (19Brown M.S. Goldstein J.L. Cell. 1997; 89: 331-340Abstract Full Text Full Text PDF PubMed Scopus (3029) Google Scholar). The precursors of SREBPs (∼125 kDa) are located in endoplasmic reticulum. Upon activation, SREBPs are released from the membrane by a sequential two-step cleavage process and translocated into the nucleus as a mature protein (∼68 kDa) (20DeBose-Boyd R.A. Brown M.S. Li W.P. Nohturfft A. Goldstein J.L. Espenshade P.J. Cell. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). is a in liver and adipose which the of gene transcription by insulin and food intake I. Goldstein J.L. Brown M.S. J. 1997; PubMed Scopus Google Scholar, J. D. A. D. L. G. B. Biochem. Biophys. Res. Commun. PubMed Scopus Google Scholar, C. I. P. C. C. Spiegelman B. Kim J.B. Ferre P. Foufelle F. Cell. Biol. 1999; PubMed Scopus Google whereas is major isoform in In the study, we that ACCβ gene transcription by promoter II is in liver by the intake of diet. the of SREBP-1 ACCβ promoter II by its binding to SREs and food intake increases the of in ACCβ promoter II in liver. for and from assay was from and from in transcription and assay from assay was from and from and used for For fasting and for and with a for or at The and the for from and cells in minimal essential with and at in for at cells a and for cells with the to the the and of in of and to of of The of in transfection was to the by of The cells with and with of the into The cells for with the with and in with and the cells and by 200 of and was by activities of and of assay For the of at was at J. Scholar). of by the activities by the of expression of is by of cells in with and at For cells at a of and the by the The of or was with of expression as with of For of the was to of and at for The cells at transfection and and activities of of was from liver of which was or for the by to the the in was in and by of of from two animals of of with MOPS, and to in a and to The to of the rat ACCβ gene was with the and used as a The with the for at with the membrane was with at for by at for The membrane was to with at liver was in with a and for The was to the and protein of the was with in and to was with or and for or to of used as for of by was by by with with from rat liver was with in of at for The was by of the of in I and at for from by of of and for at with and with of at for and and to at with was in the to the of the I the region from to in by with a of which is with The of the for and of SREBP-1 as in 17Moon Y.A. Lee J.J. Park S.W. Ahn Y.H. Kim K.S. J. Biol. Chem. 2000; 275: 30280-30286Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar, with of for the of and of and of I was to the binding of at the was by of 200 and The was with and by The in and The compared with by the cleavage of the to the to –93 to of ACCβ promoter II generated by to and to The and used in as was from the The to was as of a was at the by with and of at for of was to the and to for by to was by the through a For EMSA, the with SREBP-1 or liver in a of of and of at the a in at for at the was and to for at with of of ACCβ promoter II in Lee J.J. Y.A. Ahn Y.H. Kim K.S. J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). ACCβ promoter I was with and and in and the site of ACCβ promoter I and promoter II by rat and the of and rat ACCβ promoter I and II into and sites of The expression and by of of and into the site of the The expression was the from of and the was the from S. of assay was modified from the by M.E. L. J. Biol. Chem. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). from the and with with for at a rate of through the with in for at the with for and the liver was and in The of liver was and in the of liver is markedly to the of liver was with of and by at for at was in of the was for with of in at and at for at and 200 of was into for in the of for of was for in with at the of of chromatin with of of protein 200 a which the and the was to a The of or to chromatin and for at a with of of protein 200 for at by at for at The for in and with from the in with of at the 200 was and the at for at for the of the with and was with of and of The by for at in of and at of control or used as a in the for ACCβ promoter I or ACCβ promoter II The of where the of the of to in a and by of ACCβ in is known to play a critical role in regulation of fatty acid β-oxidation in skeletal muscle and heart, where its malonyl-CoA the of fatty acid into mitochondria by the carnitine palmitoyl-CoA transferase I. acid oxidation rate in muscle is by regulating the phosphorylation of ACCβ in to exercise W.W. Hardie D.G. Am. J. Physiol. 1996; 270: E299-E304Crossref PubMed Google Scholar, 9Rasmussen B.B. Winder W.W. J. Appl. Physiol. 1997; 83: 1104-1109Crossref PubMed Scopus (130) Google Scholar, 10Dean D. Daugaard J.R. Young M.E. Saha A. Vavvas D. Asp S. Kiens B. Kim K.H. Witters L. Richter E.A. Ruderman N. Diabetes. 2000; 49: 1295-1300Crossref PubMed Scopus (102) Google Scholar). In contrast, the fatty acid oxidation rate in liver is but by nutritional This control in liver to that the activities of ACCβ might be mainly regulated by the enzyme contents the phosphorylation this we have ACCβ expression in protein and mRNA in and The of the in the induction of two of about in by The of two to the of ACC and in liver from for ACC induction in rat liver is to be the that the of the of which 200 not by food which of two is ACCβ, we the with the the of The in amino acid of ACCβ from ACCα is the additional NH2-terminal 200 amino acids in ACCβ, known as a mitochondrial signal (3Ha J. Lee J.K. Kim K.S. Witters L.A. Kim K.H. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 11466-11470Crossref PubMed Scopus (132) Google Scholar, 4Abu-Elheiga L. Brinkley W.R. Zhong L. Chirala S.S. Woldegiorgis G. Wakil S.J. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 1444-1449Crossref PubMed Scopus (329) Google Scholar). only the with of the two was by These data that the of ACCβ, for which has been the of the major of are markedly increased in liver by food intake as as of this induction of ACCβ protein the increase of its mRNA in liver, was with the to ACCβ the from of as the The ACCβ mRNA was increased food intake, and was to be markedly increased at These suggest that the expression of ACCβ is at the transcriptional level in liver. for ACCβ mRNA in and the of ACCβ to ACCβ gene is known to be by two of and D. Apazidis A. Saha A.K. Gamble J. Patel A. Kemp B.E. Witters L.A. Ruderman N.B. J. Biol. Chem. 1997; 272: 13255-13261Abstract Full Text Full Text PDF PubMed Scopus (348) Google Scholar). which of two the expression of the ACCβ gene in liver, we have the 5′-untranslated region of ACCβ from rat liver by of or which to is as I and II for and as in The of the in and and the of in and The of from with markedly increased in rat with the of of ACCβ The of I around nucleotides in to the region of the whereas of II showed major around nucleotides These data suggest that promoter II mainly the expression of ACCβ in rat liver and is by food Most lipogenic enzymes, as fatty acid synthase, ATP citrate-lyase, and ACCα, in liver by the intake of and is to be a main mediator M.K. Lopez J.M. Sanchez H.B. Osborne T.F. J. Biol. Chem. 1995; 270: 25578-25583Abstract Full Text Full Text PDF PubMed Scopus (334) Google Scholar, 17Moon Y.A. Lee J.J. Park S.W. Ahn Y.H. Kim K.S. J. Biol. Chem. 2000; 275: 30280-30286Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar, 18Andreolas C. da Silva Xavier G. Diraison F. Zhao C. Varadi A. Lopez-Casillas F. Ferre P. Foufelle F. Rutter G.A. Diabetes. 2002; 51: 2536-2545Crossref PubMed Scopus (55) Google Scholar). we have the to SREBP-1 ACCβ of markedly only promoter II of and rat ACCβ but not promoter I These data that promoter II is the promoter for regulated expression of ACCβ by SREBP-1 in rat liver. of SREBP-1 in the region SREBP-1 the transient transfection with of ACCβ promoter II of increased the promoter The of the to –93 not change the SREBP-1 responsiveness of the with a increase in the of the of the to –38 markedly the promoter by SREBP-1 to the of the promoter II. The of the region from –38 to including the almost the promoter This data that the region from –93 to –38 plays important role in responsiveness of ACCβ promoter II to SREBP-1. of SREBP-1 in II of ACCβ the of the SREBP-1 binding region in the ACCβ promoter II, I assay was The region from to was from I by SREBP-1, the binding of SREBP-1. The region around the is conserved and rat and two for binding in as and by In is conserved and in For EMSA, the wild and in generated by with the and ACCβ the activities of including wild and the the in in might be by in the of SREBP-1 to The and a with SREBP-1, resulting in the single The of the SREBP-1 but the of the with SREBP-1. The of and almost the SREBP-1 These that SREBP-1 has to and to and to the region of the ACCβ promoter II. of and rat ACCβ promoter II and of wild and used in for and SREBP-1 binding are marked the and regions of rat are In rat SREs The of the to to and the of are also in A. of wild and generated by the and from the The with of SREBP-1. binding to The and the from rat liver in the of or of The region from to in rat promoter with as the binding site for and in a as ATP citrate-lyase, and genes P.A. Brown M.S. Goldstein J.L. J. Biol. Chem. Full Text PDF PubMed Google Scholar, Y.A. Park S.W. Kim K.S. 2002; PubMed Scopus Google Scholar, S.S. J. Lipid Res. Full Text Full Text PDF PubMed Google Scholar). In this region is also conserved except for the to the binding of to this promoter we with the from to of the This major by with rat liver and the was by The of to the binding not These data suggest that this of in and rat we the of SREBP-1 responsiveness of promoter II The stimulation of promoter of by SREBP-1 was about by the in The in also in marked inhibition of The of and almost SREBP-1 These data that and play a critical role in induction of ACCβ Interestingly, the at the binding site markedly promoter and the of this region not of promoter The the is by at the binding site not be by in the the role of the binding for SREBP-1 stimulation in ACCβ promoter II, the transient transfection assay in the was The of markedly increased gene expression in the whereas the of the Sp1-binding this The of also increased activities in wild and but of The of with or showed the of the gene in the wild type but not in the These data that binding to is essential for stimulation of ACCβ promoter II. SREBP-1 in ACCβ II by in we have assay to SREBP-1 to ACCβ gene promoter II is in rat by dietary The was to the transcription factors binding to by of into the to SREBP-1 was used to the and the of the ACCβ gene was by The of SREBP-1 to promoter I was not in the and In the the of promoter II increased to the of chromatin by of whereas the not in the The of in which used for almost the to of in and These that the the region of promoter II by SREBP-1 is regulated in vivo by status and this regulation might the control of ACCβ gene expression in liver by diet. The of the NH2-terminal amino acid of ACCβ is and has a role ACCβ to the outer membrane of mitochondria (4Abu-Elheiga L. Brinkley W.R. Zhong L. Chirala S.S. Woldegiorgis G. Wakil S.J. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 1444-1449Crossref PubMed Scopus (329) Google Scholar). The mitochondrial ACCβ to control malonyl-CoA around which is the factor of mitochondrial fatty acid The of ACCβ in muscle is by the but not by of enzyme W.W. Hardie D.G. Am. J. Physiol. 1996; 270: E299-E304Crossref PubMed Google Scholar, 9Rasmussen B.B. Winder W.W. J. Appl. Physiol. 1997; 83: 1104-1109Crossref PubMed Scopus (130) Google Scholar, 11Vavvas D. Apazidis A. Saha A.K. Gamble J. Patel A. Kemp B.E. Witters L.A. Ruderman N.B. J. Biol. Chem. 1997; 272: 13255-13261Abstract Full Text Full Text PDF PubMed Scopus (348) Google (7Minokoshi Y. Kim Y.B. Peroni O.D. Fryer L.G. Muller C. Carling D. Kahn B.B. Nature. 2002; 415: 339-343Crossref PubMed Scopus (1691) Google or Saha A.K. C. Ruderman N.B. Proc. Natl. Acad. Sci. U. S. A. 2002; PubMed Scopus Google increase phosphorylation of ACCβ by protein of ACCβ to inhibition of its and malonyl-CoA around a the of carnitine palmitoyl-CoA transferase I is and β-oxidation be acid oxidation in liver is by nutritional not by fasting markedly increases the fatty acid from adipose tissue to liver, where fatty acids to acetyl-CoA for ketone The ketone oxidation of fatty acid in liver is to be regulated by ACCβ, the ACCβ in in the of (13Abu-Elheiga L. Matzuk M.M. Abo-Hashema K.A. Wakil S.J. Science. 2001; 291: 2613-2616Crossref PubMed Scopus (752) Google Scholar). The animals lacking this enzyme showed increased food intake, of the increase of that the regulation of ACCβ activities plays a critical role in energy In the study, we revealed that fasting for almost the ACCβ in liver, whereas the food intake increases the level of this of this enzyme in liver by the dietary occurs mainly at the transcriptional level in a as the of lipogenic enzymes, as ACCα, ATP citrate-lyase, and M.E. Lopez-Casillas F. Kim K.H. J. Biol. Chem. Full Text PDF PubMed Google Scholar, K.S. Park S.W. Kim J. PubMed Scopus Google Scholar, K.S. Park S.W. Kim Biochem. Biophys. Res. Commun. PubMed Scopus Google Scholar). These facts suggest that the increased of of ACCβ might in from of fatty acid and its oxidation during the in liver as as from the increased β-oxidation of fatty acid in muscle. was that the ACCβ gene has the two promoters, as promoter I and II. promoter II to muscle regulatory as and which to control the gene expression J.J. Y.A. Ahn Y.H. Kim K.S. J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar, Lee J.J. Kim K.S. Scholar). In the study, revealed that promoter II is a promoter in liver and by the intake of diet. ACCβ promoter II is by of SREBP-1, which is known to play a critical role in dietary control of lipogenic enzyme genes (14Tabor D.E. Kim J.B. Spiegelman B.M. Edwards P.A. J. Biol. Chem. 1999; 274: 20603-20610Abstract Full Text Full Text PDF PubMed Scopus (199) Google Scholar, 15Magana M.M. Lin S.S. Dooley K.A. Osborne T.F. J. Lipid Res. 1997; 38: 1630-1638Abstract Full Text PDF PubMed Google Scholar, 16Bennett M.K. Lopez J.M. Sanchez H.B. Osborne T.F. J. Biol. Chem. 1995; 270: 25578-25583Abstract Full Text Full Text PDF PubMed Scopus (334) Google Scholar, 17Moon Y.A. Lee J.J. Park S.W. Ahn Y.H. Kim K.S. J. Biol. Chem. 2000; 275: 30280-30286Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar, 18Andreolas C. da Silva Xavier G. Diraison F. Zhao C. Varadi A. Lopez-Casillas F. Ferre P. Foufelle F. Rutter G.A. Diabetes. 2002; 51: 2536-2545Crossref PubMed Scopus (55) Google Scholar). promoter I does not to SREBP-1 at I and revealed the sites and and Sp1-binding site SREBP-1 showed to and the in or in and in SREBP-1 The of and almost SREBP-1 These data that and play a major role in SREBP-1 ACCβ promoter II. The of the SREBP-1 in cells and the of ACCβ promoter II by and SREBP-1 in we that binding to is by SREBP-1 at and for the of the ACCβ gene. These the of and SREBP-1 in the transcription in genes S.S. J. Lipid Res. Full Text Full Text PDF PubMed Google Scholar, L. Sanchez H.B. Osborne T.F. Proc. Natl. Acad. Sci. U. S. A. 1995; PubMed Scopus Google Scholar, Sanchez H.B. Osborne T.F. Cell. Biol. 1997; 17: PubMed Scopus Google Scholar, N. Y. F. Y. J. S. S. N. J. Biol. Chem. 2000; 275: Full Text Full Text PDF PubMed Scopus Google Scholar). of the in that the region from to the binding for and SREBP-1, plays important role in of the ACCβ gene. assay in vivo showed that the of SREBP-1 is in ACCβ promoter II by the intake of a diet. This that binding to ACCβ promoter II is regulated by dietary status and be for of ACCβ gene In the study, we showed that the expression of the ACCβ gene is regulated by nutritional status at the transcriptional and binding to SREs plays the critical role in this