Molecular analysis of the human thrombin-activatable fibrinolysis inhibitor gene promoter

Mathieu Garand, Nazareth Bastajian, Michael E. Nesheim, Michael B. Boffa, Marlys L. Koschinsky

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Thrombin-activatable fibrinolysis inhibitor (TAFI) is a carboxypeptidase B-like pro-enzyme that, once activated, attenuates fibrinolysis. Little is presently known of the factors that regulate expression of CPB2, the gene encoding TAFI. This study identified 10 potential transcription factor binding sites (denoted A-J) within the proximal promoter region of CPB2, spanning nucleotides -425 to +21; two of these represent previously-described binding sites for CCAAT/enhancer binding protein and glucocorticoid receptor. We identified additional transcription factors that bind within the proximal CPB2 promoter, namely, nuclear factor-Y (NF-Y) and hepatocyte nuclear factor-1α (HNF-1α). Binding of NF-Y to the region between nucleotides -76 to -59 (Site B) is important for basal CPB2 promoter activity; NF-Y may be a key factor for the recruitment of the transcriptional machinery to the TAFI gene promoter. HNF-1α binds at the interface between Sites C and B. Transient transfections of CPB2 promoter-reporter constructs showed that HNF-1α binding is essential for the activity of this promoter in HepG2 cells, indicating that HNF-1α is involved in the liver-specific expression of CPB2.

Original languageEnglish
Pages (from-to)231-244
Number of pages14
JournalBritish Journal of Haematology
Volume138
Issue number2
DOIs
Publication statusPublished - 1 Jul 2007
Externally publishedYes

Fingerprint

Hepatocyte Nuclear Factor 1
Carboxypeptidase B2
Genes
Transcription Factors
Nucleotides
Binding Sites
Carboxypeptidase B
CCAAT-Enhancer-Binding Proteins
Glucocorticoid Receptors
Hep G2 Cells
Fibrinolysis
Genetic Promoter Regions
Transfection
Gene Expression
Liver
Enzymes
nuclear factor Y

Keywords

  • Fibrinolysis
  • Gene regulation
  • Liver
  • Thrombin-activatable fibrinolysis inhibitor
  • Transcription

ASJC Scopus subject areas

  • Hematology

Cite this

Molecular analysis of the human thrombin-activatable fibrinolysis inhibitor gene promoter. / Garand, Mathieu; Bastajian, Nazareth; Nesheim, Michael E.; Boffa, Michael B.; Koschinsky, Marlys L.

In: British Journal of Haematology, Vol. 138, No. 2, 01.07.2007, p. 231-244.

Research output: Contribution to journalArticle

Garand, Mathieu ; Bastajian, Nazareth ; Nesheim, Michael E. ; Boffa, Michael B. ; Koschinsky, Marlys L. / Molecular analysis of the human thrombin-activatable fibrinolysis inhibitor gene promoter. In: British Journal of Haematology. 2007 ; Vol. 138, No. 2. pp. 231-244.
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