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Thromb Haemost 2003; 90(06): 1029-1039
DOI: 10.1160/TH03-07-0443
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Characterization of the human protein S gene promoter: a possible role of transcription factors Sp1 and HNF3 in liver

Hideki Tatewaki
1   Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
,
Hiroko Tsuda
1   Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
,
Taisuke Kanaji
1   Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
,
Kazunari Yokoyama
2   Tsukuba Life Science Center, The Institute of Physical and Chemical Research (RIKEN), Ibaraki, Japan
,
Naotaka Hamasaki
1   Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
› InstitutsangabenFinancial support: This work was supported in part by grants from the Ministry of Education, Science, Sports, and Culture of Japan (to NH) and by grants from the Magnetic Health Science Foundation (to NH).
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Publikationsverlauf

Received 07. Juli 2003

Accepted after revision 18. August 2003

Publikationsdatum:
05. Dezember 2017 (online)

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Summary

Protein S is a vitamin-K-dependent plasma glycoprotein that serves as a cofactor for activated protein C in the protein C anticoagulation pathway, which regulates blood coagulation by inactivating factors Va and VIIIa. Mechanisms regulating the expression of the protein S gene remain unknown to date. The aim of this study was to characterize the cis-acting DNA elements of the human protein S gene in liver.

We found that liver cell lines (HepG2 and PLC) transcribed the human protein S gene to mRNA, whereas non-liver cell lines (HEK293 and HeLa cells) either transcribed the gene weakly or not at all. Isolation and analysis of tissue-specific gene expression in HepG2 and HeLa cells of the 5’-flanking region from-6183 to +294 of the protein S gene indicated that the consensus binding motifs to HNF3 and Sp1 or MAZ transcription factors in the flanking region are essential for protein S gene expression. Exogenous expression of the Sp1 gene augmented the protein S-reporter gene expression in HepG2 or PLC cells but had no effect in HeLa cells. Taken together, we would conclude that transcription factors of HNF3, MAZ, and Sp1 are required for high-level expression of the protein S gene in hepatic cells, but in non-hepatic cells such as HeLa cells, an unknown factor(s) binds to the Sp1 region and disturbs the action of Sp1 and MAZ.

Keywords

Gene expression - protein C/S pathway - transcription factors
 

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