THE ROLE OF THE CCAAT ENHANCER-BINDING PROTEIN IN THE TRANSCRIPTIONAL REGULATION OF THE GENE FOR PHOSPHOENOLPYRUVATE CARBOXYKINASE (GTP)

被引:210
作者
PARK, EA [1 ]
ROESLER, WJ [1 ]
LIU, J [1 ]
KLEMM, DJ [1 ]
GURNEY, AL [1 ]
THATCHER, JD [1 ]
SHUMAN, J [1 ]
FRIEDMAN, A [1 ]
HANSON, RW [1 ]
机构
[1] CARNEGIE INST WASHINGTON,DEPT EMBRYOL,HOWARD HUGHES RES LABS,BALTIMORE,MD 21210
关键词
D O I
10.1128/MCB.10.12.6264
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Previous studies have identified a region in the promoter of the gene for phosphoenolpyruvate carboxykinase (GTP) (PEPCK) (positions -460 to +73) containing the regulatory elements which respond to cyclic AMP, glucocorticoids, and insulin and confer the tissue- and developmental stage-specific properties to the gene. We report that CCAAT/enhancer-binding protein (C/EBP) binds to the cyclic AMP-responsive element CRE-1 as well as to two regions which have been previously shown to bind proteins enriched in liver nuclei. The DNase I footprint pattern provided by the recombinant C/EBP was identical to that produced by a 43-k Da protein purified from rat liver nuclear extracts, using a CRE oligonucleotide affinity column, which was originally thought to be the CRE-binding protein CREB. Transient cotransfection experiments using a C/EBP expression vector demonstrated that C/EBP could trans activate the PEPCK promoter. The trans activation occurred through both the upstream, liver-specific protein-binding domains and the CRE. The CRE-binding protein bound only to CRE-1 and not to the upstream C/EBP-binding sites. The results of this study, along with physiological properties of C/EBP, indicate an important role for this transcription factor in providing the PEPCK gene with several of its regulatory characteristics.
引用
收藏
页码:6264 / 6272
页数:9
相关论文
共 34 条
  • [1] Ausubel F.M., Brent R., Kingston R.E., Moore D.D., Seidman J.G., Seidman J.A., Smith J.A., Struhl K., Current Protocols in Molecular Biology, 1, (1987)
  • [2] Benvenisty N., Nechushtan H., Cohen H., Reshef L., Separate cis-regulatory elements confer expression of phos-phoenolpyruvate carboxykinase (GTP) gene in different cell lines, Proc. Natl. Acad. Sci. USA, 86, pp. 1118-1122, (1989)
  • [3] Birkenmeier E.H., Gwynn B., Howard S., Jerry J., Gordan J.L., Landschultz W.H., McKnight S.L., Tissue-specific expression, developmental regulation and genetic mapping of the gene encoding CCAAT/enhancer binding protein, Genes Dev., 3, pp. 1146-1156, (1989)
  • [4] Bokar J.A., Roesler W.J., Vandenbark G.R., Kaetzel D.M., Hanson R.W., Nilson J.H., Characterization of the cAMP responsive elements from the genes for the α-subunit of glycoprotein hormones and phosphoenolpyruvate carboxykinase (GTP), J. Biol. Chem., 263, pp. 19740-19747, (1988)
  • [5] Christy R.J., Yang V.W., Ntambi J.M., Geiman D.E., Landschultz W.H., Friedman A.D., Nakabeppu Y., Kelly T.J., Lane M.D., Differentiation-induced gene expression in 3T3-L1 preadipocytes: CCAAT/enhancer binding protein interacts with and activates the promoters of two adipocyte-specific genes, Genes Dev., 3, pp. 1323-1335, (1989)
  • [6] Friedman A.D., Landschultz W.H., McKnight S.L., CCAAT/enhancer binding protein activates the promoter of the serum albumin gene in cultured hepatoma cells, Genes Dev., 3, pp. 1314-1322, (1989)
  • [7] Gonzalez G.A., Yamamoto K.K., Fischer W.H., Karr D., Menzel P., Biggs W., Vale W.W., Montminy M.R., A cluster of phosphorylation sites on the cyclic-AMP regulated nuclear factor CREB predicted by its sequence, Nature (London), 337, pp. 749-752, (1989)
  • [8] Gorman C.M., Moffat L.F., Howard B.H., Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells, Mol. Cell. Biol., 2, pp. 1044-1051, (1982)
  • [9] Gorski K., Carneiro M., Schibler U., Tissue-specific in vitro transcription from the mouse albumin promoter, Cell, 47, pp. 767-776, (1986)
  • [10] Hai T., Liu F., Coukos W.J., Green M.R., Transcription factor ATF cDNA clones: An extensive family of leucine zipper proteins able to selectively form DNA-protein heterodimers, Genes Dev., 3, pp. 2083-2090, (1989)