SYNERGISTIC TRANSACTIVATION OF THE HUMAN C-REACTIVE PROTEIN PROMOTER BY TRANSCRIPTION FACTOR HNF-1 BINDING AT 2 DISTINCT SITES

被引:118
作者
TONIATTI, C
DEMARTIS, A
MONACI, P
NICOSIA, A
CILIBERTO, G
机构
[1] FAC MED & CHIRURG,DIPARTIMENTO BIOCHIM & BIOTECNOL MED,I-80131 NAPLES,ITALY
[2] CTR INGN GENET,I-80131 NAPLES,ITALY
关键词
C-REACTIVE PROTEIN; LIVER SPECIFIC GENE EXPRESSION; TRANSCRIPTION FACTOR HNF-1; TRANSACTIVATION;
D O I
10.1002/j.1460-2075.1990.tb07897.x
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
The promoter region of the human C-reactive protein (CPR) gene comprises two distinct regions (APREs, for Acute Phase Responsive Elements) each one containing information necessary and sufficient for liver specific and IL-6 inducible expression in human hepatoma Hep3B cells. In this paper we show that both APREs contain a low affinity binding site for the liver specific transcription factor HNF-1/LF-B1. The two sites are separated by approximately 80 bp. Mutations in either of the two sites abolish inducible expression. The same effect is specifically obtained in cotransfection competition experiments when the human albumin HNF-1 site is used as competitor. However, HNF-1 is not the intranuclear mediator of IL-6 because synthetic promoters formed by multimerized copies of different HNF-1 binding sites are not transcriptionally activated by this cytokine. An expression vector encoding full length HNF-1 is capable of trans-activating transcription from the wild-type CPR promoter but not from mutants which have lost the ability to bind HNF-1. Moreover, the level of trans-activation observed with the natural promoter containing both HNF-1 binding sites is far greater than the level of mutated variants containing only one of the two sites. This result strongly suggests that two HNF-1 molecules bound simultaneously to sites distant from each other can act synergistically to activate gene expression.
引用
收藏
页码:4467 / 4475
页数:9
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