Identification of a glucocorticoid response element in the human γ chain fibrinogen promoter

被引:14
作者
Asselta, R [1 ]
Duga, S [1 ]
Modugno, M [1 ]
Malcovati, M [1 ]
Tenchini, ML [1 ]
机构
[1] Univ Milan, Dipartimento Biol & Genet Sci Med, I-20133 Milan, Italy
关键词
D O I
10.1055/s-0037-1615031
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The effect of the synthetic glucocorticoid hormone dexamethasone on human gamma chain fibrinogen gene expression was examined. The whole promoter region of 3.8 kb of this gene and progressive 5'-deletions were inserted into a promoterless expression vector, upstream of the luciferase gene and transiently transfected into the human hepatoma HepG2 cells, in the presence or in the absence of dexamethasone stimulation. Deletion analysis allowed to identify a region located between -1359 and -954 bp upstream from the transcription start site, involved in hormone inducibility. On the basis of a computer-assisted analysis, a putative GRE was found in this region at bases -1116 to -1102. Specific point mutations eliminating this putative GRE led to complete loss of glucocorticoid inducibility, thus indicating its functional role. Binding of the rat glucocorticoid receptor to this site was demonstrated by mobility-shift assays.
引用
收藏
页码:1144 / 1150
页数:7
相关论文
共 45 条
[1]  
ANDERSON GM, 1993, J BIOL CHEM, V268, P22650
[2]   Mechanisms of transcriptional activation of the promoter of the rainbow trout prolactin gene by GHF1/Pit1 and glucocorticoid [J].
Argenton, F ;
Ramoz, N ;
Charlet, N ;
Bernardini, S ;
Colombo, L ;
Bortolussi, M .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1996, 224 (01) :57-66
[3]  
BAUMANN H, 1989, ANN NY ACAD SCI, V557, P280
[4]  
BAUMANN H, 1990, J BIOL CHEM, V265, P22275
[5]   GENE-REGULATION BY STEROID-HORMONES [J].
BEATO, M .
CELL, 1989, 56 (03) :335-344
[6]   FIBRINOGEN STRUCTURE, ACTIVATION, POLYMERIZATION AND FIBRIN GEL STRUCTURE [J].
BLOMBACK, B .
THROMBOSIS RESEARCH, 1994, 75 (03) :327-328
[7]   DISTINCT SEQUENCE ELEMENTS INVOLVED IN THE GLUCOCORTICOID REGULATION OF THE MOUSE MAMMARY-TUMOR VIRUS PROMOTER IDENTIFIED BY LINKER SCANNING MUTAGENESIS [J].
BUETTI, E ;
KUHNEL, B .
JOURNAL OF MOLECULAR BIOLOGY, 1986, 190 (03) :379-389
[8]   TRANSCRIPTIONAL CONTROL OF HUMAN PAPILLOMAVIRUS (HPV) ONCOGENE EXPRESSION - COMPOSITION OF THE HPV TYPE-18 UPSTREAM REGULATORY REGION [J].
BUTZ, K ;
HOPPESEYLER, F .
JOURNAL OF VIROLOGY, 1993, 67 (11) :6476-6486
[9]   MULTIPLE HEPATOCYTE-ENRICHED NUCLEAR FACTORS FUNCTION IN THE REGULATION OF TRANSTHYRETIN AND ALPHA-1-ANTITRYPSIN GENES [J].
COSTA, RH ;
GRAYSON, DR ;
DARNELL, JE .
MOLECULAR AND CELLULAR BIOLOGY, 1989, 9 (04) :1415-1425
[10]   THE HUMAN BETA-FIBRINOGEN PROMOTER CONTAINS A HEPATOCYTE NUCLEAR FACTOR 1-DEPENDENT INTERLEUKIN-6-RESPONSIVE ELEMENT [J].
DALMON, J ;
LAURENT, M ;
COURTOIS, G .
MOLECULAR AND CELLULAR BIOLOGY, 1993, 13 (02) :1183-1193