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. 2001 Aug 15;358(Pt 1):127–135. doi: 10.1042/0264-6021:3580127

Genomic distribution of three promoters of the bovine gene encoding acetyl-CoA carboxylase alpha and evidence that the nutritionally regulated promoter I contains a repressive element different from that in rat.

J Mao 1, S Marcos 1, S K Davis 1, J Burzlaff 1, H M Seyfert 1
PMCID: PMC1222040  PMID: 11485560

Abstract

The enzyme acetyl-CoA carboxylase alpha (ACC-alpha) is rate-limiting for the synthesis of long-chain fatty acids de novo. As a first characterization of the bovine gene encoding this enzyme, we established the entire bovine ACC-alpha cDNA sequence (7041 bp) and used experiments with 5' rapid amplification of cDNA ends to determine the heterogeneous composition of 5' untranslated regions, as expressed from three different promoters (PI, PII and PIII). The individual locations of these promoters have been defined within an area comprising 35 kbp on Bos taurus chromosome 19 ('BTA19'), together with the segmentation of the first 14 exons. Primer extension analyses reveal that the nutritionally regulated PI initiates transcription from at least four sites. PI transcripts are much more abundant in adipose and mammary-gland tissues than in liver or lung. A 2.6 kb promoter fragment drives the expression of reporter genes only weakly in different model cells, irrespective of stimulation with insulin or dexamethasone. Thus bovine PI is basically repressed, like its analogue from rat. Finely graded deletions of PI map two separate elements, which have to be present together in cis to repress bovine PI. The distal component resides within a well-preserved Art2 retroposon element. Thus sequence, structure and evolutionary origin of the main repressor of PI in bovines are entirely different from its functional counterpart in rat, which had been identified as a (CA)(28) microsatellite. We show that, in different mammalian species, unrelated genome segments of different origins have been recruited to express as functionally homologous PI the ancient and otherwise highly conserved ACC-alpha-encoding gene.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abu-Elheiga L., Jayakumar A., Baldini A., Chirala S. S., Wakil S. J. Human acetyl-CoA carboxylase: characterization, molecular cloning, and evidence for two isoforms. Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):4011–4015. doi: 10.1073/pnas.92.9.4011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barber M. C., Travers M. T. Cloning and characterisation of multiple acetyl-CoA carboxylase transcripts in ovine adipose tissue. Gene. 1995 Mar 10;154(2):271–275. doi: 10.1016/0378-1119(94)00871-o. [DOI] [PubMed] [Google Scholar]
  3. Barber M. C., Travers M. T. Elucidation of a promoter activity that directs the expression of acetyl-CoA carboxylase alpha with an alternative N-terminus in a tissue-restricted fashion. Biochem J. 1998 Jul 1;333(Pt 1):17–25. doi: 10.1042/bj3330017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Batenburg J. J., Whitsett J. A. Levels of mRNAs coding for lipogenic enzymes in rat lung upon fasting and refeeding and during perinatal development. Biochim Biophys Acta. 1989 Dec 18;1006(3):329–334. doi: 10.1016/0005-2760(89)90020-9. [DOI] [PubMed] [Google Scholar]
  5. Bendall A. J., Molloy P. L. Base preferences for DNA binding by the bHLH-Zip protein USF: effects of MgCl2 on specificity and comparison with binding of Myc family members. Nucleic Acids Res. 1994 Jul 25;22(14):2801–2810. doi: 10.1093/nar/22.14.2801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brownsey R. W., Zhande R., Boone A. N. Isoforms of acetyl-CoA carboxylase: structures, regulatory properties and metabolic functions. Biochem Soc Trans. 1997 Nov;25(4):1232–1238. doi: 10.1042/bst0251232. [DOI] [PubMed] [Google Scholar]
  7. Cai L., Taylor J. F., Wing R. A., Gallagher D. S., Woo S. S., Davis S. K. Construction and characterization of a bovine bacterial artificial chromosome library. Genomics. 1995 Sep 20;29(2):413–425. doi: 10.1006/geno.1995.9986. [DOI] [PubMed] [Google Scholar]
  8. Carlson C. A., Kim K. H. Regulation of hepatic acetyl coenzyme A carboxylase by phosphorylation and dephosphorylation. Arch Biochem Biophys. 1974 Oct;164(2):478–489. doi: 10.1016/0003-9861(74)90058-7. [DOI] [PubMed] [Google Scholar]
  9. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  10. Don R. H., Cox P. T., Wainwright B. J., Baker K., Mattick J. S. 'Touchdown' PCR to circumvent spurious priming during gene amplification. Nucleic Acids Res. 1991 Jul 25;19(14):4008–4008. doi: 10.1093/nar/19.14.4008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Duncan C. H. Novel Alu-type repeat in artiodactyls. Nucleic Acids Res. 1987 Feb 11;15(3):1340–1340. doi: 10.1093/nar/15.3.1340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. El Khadir-Mounier C., Le Fur N., Powell R. S., Diot C., Langlois P., Mallard J., Douaire M. Cloning and characterization of the 5' end and promoter region of the chicken acetyl-CoA carboxylase gene. Biochem J. 1996 Mar 1;314(Pt 2):613–619. doi: 10.1042/bj3140613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Eritani N., Fukuda H., Matsumura Y. Lipogenic enzyme gene expression in rat liver during development after birth. J Biochem. 1993 May;113(5):519–525. doi: 10.1093/oxfordjournals.jbchem.a124076. [DOI] [PubMed] [Google Scholar]
  14. Gilmore T. D. NF-kappa B, KBF1, dorsal, and related matters. Cell. 1990 Sep 7;62(5):841–843. doi: 10.1016/0092-8674(90)90257-f. [DOI] [PubMed] [Google Scholar]
  15. Guo B., Odgren P. R., van Wijnen A. J., Last T. J., Nickerson J., Penman S., Lian J. B., Stein J. L., Stein G. S. The nuclear matrix protein NMP-1 is the transcription factor YY1. Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10526–10530. doi: 10.1073/pnas.92.23.10526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ha J., Daniel S., Kong I. S., Park C. K., Tae H. J., Kim K. H. Cloning of human acetyl-CoA carboxylase cDNA. Eur J Biochem. 1994 Jan 15;219(1-2):297–306. doi: 10.1111/j.1432-1033.1994.tb19941.x. [DOI] [PubMed] [Google Scholar]
  17. Hardie D. G. Regulation of fatty acid synthesis via phosphorylation of acetyl-CoA carboxylase. Prog Lipid Res. 1989;28(2):117–146. doi: 10.1016/0163-7827(89)90010-6. [DOI] [PubMed] [Google Scholar]
  18. Henke M., Hobom G., Senft B., Seyfert H. M. Structural deviations in a bovine low expression lysozyme-encoding gene active in tissues other than stomach. Gene. 1996 Oct 31;178(1-2):131–137. doi: 10.1016/0378-1119(96)00352-6. [DOI] [PubMed] [Google Scholar]
  19. Javahery R., Khachi A., Lo K., Zenzie-Gregory B., Smale S. T. DNA sequence requirements for transcriptional initiator activity in mammalian cells. Mol Cell Biol. 1994 Jan;14(1):116–127. doi: 10.1128/mcb.14.1.116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kim J. L., Nikolov D. B., Burley S. K. Co-crystal structure of TBP recognizing the minor groove of a TATA element. Nature. 1993 Oct 7;365(6446):520–527. doi: 10.1038/365520a0. [DOI] [PubMed] [Google Scholar]
  21. Kim K. H. Regulation of mammalian acetyl-coenzyme A carboxylase. Annu Rev Nutr. 1997;17:77–99. doi: 10.1146/annurev.nutr.17.1.77. [DOI] [PubMed] [Google Scholar]
  22. Koczan D., Hobom G., Seyfert H. M. Genomic organization of the bovine alpha-S1 casein gene. Nucleic Acids Res. 1991 Oct 25;19(20):5591–5596. doi: 10.1093/nar/19.20.5591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Luo X. C., Kim K. H. An enhancer element in the house-keeping promoter for acetyl-CoA carboxylase gene. Nucleic Acids Res. 1990 Jun 11;18(11):3249–3254. doi: 10.1093/nar/18.11.3249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Luo X. C., Park K., Lopez-Casillas F., Kim K. H. Structural features of the acetyl-CoA carboxylase gene: mechanisms for the generation of mRNAs with 5' end heterogeneity. Proc Natl Acad Sci U S A. 1989 Jun;86(11):4042–4046. doi: 10.1073/pnas.86.11.4042. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. López-Casillas F., Bai D. H., Luo X. C., Kong I. S., Hermodson M. A., Kim K. H. Structure of the coding sequence and primary amino acid sequence of acetyl-coenzyme A carboxylase. Proc Natl Acad Sci U S A. 1988 Aug;85(16):5784–5788. doi: 10.1073/pnas.85.16.5784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. López-Casillas F., Luo X. C., Kong I. S., Kim K. H. Characterization of different forms of rat mammary gland acetyl-coenzyme A carboxylase mRNA: analysis of heterogeneity in the 5' end. Gene. 1989 Nov 30;83(2):311–319. doi: 10.1016/0378-1119(89)90117-0. [DOI] [PubMed] [Google Scholar]
  27. López-Casillas F., Ponce-Castañeda M. V., Kim K. H. In vivo regulation of the activity of the two promoters of the rat acetyl coenzyme-A carboxylase gene. Endocrinology. 1991 Aug;129(2):1049–1058. doi: 10.1210/endo-129-2-1049. [DOI] [PubMed] [Google Scholar]
  28. McNair A., Cereghini S., Brand H., Smith T., Breillat C., Gannon F. Synergistic activation of the Atlantic salmon hepatocyte nuclear factor (HNF) 1 promoter by the orphan nuclear receptors HNF4 and chicken ovalbumin upstream promoter transcription factor I (COUP-TFI). Biochem J. 2000 Dec 1;352(Pt 2):557–564. [PMC free article] [PubMed] [Google Scholar]
  29. Oberfield J. L., Collins J. L., Holmes C. P., Goreham D. M., Cooper J. P., Cobb J. E., Lenhard J. M., Hull-Ryde E. A., Mohr C. P., Blanchard S. G. A peroxisome proliferator-activated receptor gamma ligand inhibits adipocyte differentiation. Proc Natl Acad Sci U S A. 1999 May 25;96(11):6102–6106. doi: 10.1073/pnas.96.11.6102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Palmer C. N., Hsu M. H., Griffin H. J., Johnson E. F. Novel sequence determinants in peroxisome proliferator signaling. J Biol Chem. 1995 Jul 7;270(27):16114–16121. doi: 10.1074/jbc.270.27.16114. [DOI] [PubMed] [Google Scholar]
  31. Ponce-Castañeda M. V., López-Casillas F., Kim K. H. Acetyl-coenzyme A carboxylase messenger ribonucleic acid metabolism in liver, adipose tissues, and mammary glands during pregnancy and lactation. J Dairy Sci. 1991 Nov;74(11):4013–4021. doi: 10.3168/jds.S0022-0302(91)78596-2. [DOI] [PubMed] [Google Scholar]
  32. Quandt K., Frech K., Karas H., Wingender E., Werner T. MatInd and MatInspector: new fast and versatile tools for detection of consensus matches in nucleotide sequence data. Nucleic Acids Res. 1995 Dec 11;23(23):4878–4884. doi: 10.1093/nar/23.23.4878. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Seyfert H. M., Pitra C., Meyer L., Brunner R. M., Wheeler T. T., Molenaar A., McCracken J. Y., Herrmann J., Thiesen H. J., Schwerin M. Molecular characterization of STAT5A- and STAT5B-encoding genes reveals extended intragenic sequence homogeneity in cattle and mouse and different degrees of divergent evolution of various domains. J Mol Evol. 2000 Jun;50(6):550–561. doi: 10.1007/s002390010058. [DOI] [PubMed] [Google Scholar]
  34. Shi X. M., Blair H. C., Yang X., McDonald J. M., Cao X. Tandem repeat of C/EBP binding sites mediates PPARgamma2 gene transcription in glucocorticoid-induced adipocyte differentiation. J Cell Biochem. 2000 Jan;76(3):518–527. doi: 10.1002/(sici)1097-4644(20000301)76:3<518::aid-jcb18>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
  35. Stephens J. M., Morrison R. F., Wu Z., Farmer S. R. PPARgamma ligand-dependent induction of STAT1, STAT5A, and STAT5B during adipogenesis. Biochem Biophys Res Commun. 1999 Aug 19;262(1):216–222. doi: 10.1006/bbrc.1999.0889. [DOI] [PubMed] [Google Scholar]
  36. Stewart W. C., Morrison R. F., Young S. L., Stephens J. M. Regulation of signal transducers and activators of transcription (STATs) by effectors of adipogenesis: coordinate regulation of STATs 1, 5A, and 5B with peroxisome proliferator-activated receptor-gamma and C/AAAT enhancer binding protein-alpha. Biochim Biophys Acta. 1999 Nov 11;1452(2):188–196. doi: 10.1016/s0167-4889(99)00129-9. [DOI] [PubMed] [Google Scholar]
  37. Tae H. J., Luo X., Kim K. H. Roles of CCAAT/enhancer-binding protein and its binding site on repression and derepression of acetyl-CoA carboxylase gene. J Biol Chem. 1994 Apr 8;269(14):10475–10484. [PubMed] [Google Scholar]
  38. Tae H. J., Zhang S., Kim K. H. cAMP activation of CAAT enhancer-binding protein-beta gene expression and promoter I of acetyl-CoA carboxylase. J Biol Chem. 1995 Sep 15;270(37):21487–21494. doi: 10.1074/jbc.270.37.21487. [DOI] [PubMed] [Google Scholar]
  39. Takai T., Yokoyama C., Wada K., Tanabe T. Primary structure of chicken liver acetyl-CoA carboxylase deduced from cDNA sequence. J Biol Chem. 1988 Feb 25;263(6):2651–2657. [PubMed] [Google Scholar]
  40. Teglund S., McKay C., Schuetz E., van Deursen J. M., Stravopodis D., Wang D., Brown M., Bodner S., Grosveld G., Ihle J. N. Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses. Cell. 1998 May 29;93(5):841–850. doi: 10.1016/s0092-8674(00)81444-0. [DOI] [PubMed] [Google Scholar]
  41. Thampy K. G., Wakil S. J. Regulation of acetyl-coenzyme A carboxylase. II. Effect of fasting and refeeding on the activity, phosphate content, and aggregation state of the enzyme. J Biol Chem. 1988 May 5;263(13):6454–6458. [PubMed] [Google Scholar]
  42. Travers M. T., Barber M. C. Insulin-glucocorticoid interactions in the regulation of acetyl-CoA carboxylase-alpha transcript diversity in ovine adipose tissue. J Mol Endocrinol. 1999 Feb;22(1):71–79. doi: 10.1677/jme.0.0220071. [DOI] [PubMed] [Google Scholar]
  43. Travers M. T., Barber M. C. Tissue-specific control of the acetyl-CoA carboxylase gene. Biochem Soc Trans. 1997 Nov;25(4):1215–1219. doi: 10.1042/bst0251215. [DOI] [PubMed] [Google Scholar]
  44. Travers M. T., Vernon R. G., Barber M. C. Repression of the acetyl-CoA carboxylase gene in ovine adipose tissue during lactation: the role of insulin responsiveness. J Mol Endocrinol. 1997 Oct;19(2):99–107. doi: 10.1677/jme.0.0190099. [DOI] [PubMed] [Google Scholar]
  45. Wakil S. J., Stoops J. K., Joshi V. C. Fatty acid synthesis and its regulation. Annu Rev Biochem. 1983;52:537–579. doi: 10.1146/annurev.bi.52.070183.002541. [DOI] [PubMed] [Google Scholar]
  46. Wang D., Sul H. S. Upstream stimulatory factor binding to the E-box at -65 is required for insulin regulation of the fatty acid synthase promoter. J Biol Chem. 1997 Oct 17;272(42):26367–26374. doi: 10.1074/jbc.272.42.26367. [DOI] [PubMed] [Google Scholar]
  47. Welte T., Garimorth K., Philipp S., Doppler W. Prolactin-dependent activation of a tyrosine phosphorylated DNA binding factor in mouse mammary epithelial cells. Mol Endocrinol. 1994 Aug;8(8):1091–1102. doi: 10.1210/mend.8.8.7527899. [DOI] [PubMed] [Google Scholar]

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