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Nucleic Acids Research, 1992, Vol. 20, No. 12 3091-3098
© 1992


MOLECULAR BIOLOGY

Molecular cloning of two C/EBP-related proteins that bind to the promoter and the enhancer of the {alpha}1-fetoprotein gene. Further analysis of C/EBPß and C/EBP{gamma}

Hélène Thomassin+, Diane Hamel, Daniel Bernier, Michel Guertin§ and Luc Belanger*

Le Centre de Recherche en Cancérologie de I'Université Laval, L'Hôtel-Dieu de Québec Québec G1R 2J6, Canada

* To whom correspondence should be addressed

Received March 6, 1992. Revised May 7, 1992. Accepted May 7, 1992.

In an attempt to identify proteins that may regulate {alpha}1-fetoprotein (AFP) gene expression, we screened a cDNA expression library from neonatal rat liver with two essential cis-elements of the AFP promoter and enhancer. We isolated two cDNAs which were found to correspond to leucine zipper proteins of the CC-AAT/enhancer binding protein (C/EBP) family: C/EBPß and C/EBP{gamma}. The three related proteins C/EBP {alpha}, ß and {gamma} bind with indistinguishable specificity to multiple DNA sites in the promoter and the enhancer of the AFP gene. In addition, C/EBPß and C/EBP{gamma} readily heterodimerize with each other as well as with C/EBP{alpha}. The mRNAs coding for C/EBPß and C/EBP{gamma} are expressed in a wider variety of rat tissues than C/EBP{alpha} mRNA, including yolk sac and fetal liver. The steady-state levels of C/EBP {alpha}, ß and {gamma} mRNAs increase during liver development, in parallel with their respective gene transcriptional rates. The high levels of C/EBP ß and {gamma} mRNAs in rat yolk sac and fetal liver, where C/EBP{alpha} is poorly expressed, suggest that C/EBP ß and/or {gamma} could be preponderant or early regulators of the AFP gene in these tissues.


+ Present address: Centre de Recherche sur I'Endocrinologie Moléculaire et le Développement, CNRS, UPR 1511, 9 rue Jules Hetzel, 92190 Meudon, France

* Present address: Département de Biochimie, Faculté des Sciences et Génie, Université Laval, Québec, Canada


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