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Nucleic Acids Research, 1992, Vol. 20, No. 12 3099-3104
© 1992

MOLECULAR BIOLOGY

The liver-specific promoter of the human insulin-like growth factor II gene is activated by CCAAT/enhancer binding protein (C/EBP)

M.A. van Dijk, R.J.T. Rodenburg, P. Holthuizen and J.S. Sussenbach*

Laboratory for Physiological Chemistry, State University of Utrecht Vondellaan 24a, 3521GG Utrecht, The Netherlands

* To whom correspondence should be addressed

Received March 2, 1992. Revised May 14, 1992. Accepted May 14, 1992.

The human gene coding for insulin-like growth factor II (IGF-II) contains four promoters (P1 - P4), that are subjected to tissue-specific and development-dependent regulation. Expression of promoter P1 Is detected only in adult liver tissue, whereas promoter P3 is the major IGF-II promoter in fetal liver and is further expressed in other fetal tissues and in adult non-hepatic tissues. C/EBP is a tissue- and development-specific transcription factor that is expressed predominantly in adult liver, adipose tissue and lung. The effect of C/EBP on the expression of constructs containing IGF-II promoter P1 or P3 linked to the luciferase gene was investigated in cotransfection assays using Hep3B cells. We found that promoter P1 can be activated by C/EBP, whereas this transcription factor has no effect on the expression of promoter P3. By gel retardation and DNasel footprinting it was demonstrated that C/EBP can bind to a region of P1 located between 82 and 109 basepairs upstream of the cap site. Furthermore, we showed that deletion of this C/EBP binding region strongly reduces the ability of C/EBP to stimulate transcription from P1. These results indicate that C/EBP is a major component in the specific activation of the human IGF-II promoter P1 in adult liver.


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