L. Li et Wsl. Liao, An upstream repressor element that contributes to hepatocyte-specific expression of the rat serum amyloid A1 gene, BIOC BIOP R, 264(2), 1999, pp. 395-403
Citations number
57
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Serum amyloid A (SAA) is a major acute-phase protein whose expression can b
e dramatically induced in response to tissue damage, infection, and inflamm
ation. Its expression is highly tissue-specific, restricted almost exclusiv
ely to liver hepatocytes. We have shown that a 320-bp fragment of the rat S
AA1 promoter could confer liver-cell-specific expression on a reporter gene
when transfected into cultured cells. Here we report the identification of
a 29-bp regulatory element that possesses inhibitory activities on SAA1 pr
omoter in HeLa cells but has no such effects in liver cells, Moreover, this
regulatory element has properties of a transcriptional repressor; in that,
it can function with a heterologous promoter and is independent of orienta
tion and distance from the transcription initiation site. Protein binding s
tudies showed that this regulatory element can form specific protein-DNA co
mplexes with nuclear proteins from several nonliver cell lines (HeLa, 10T(1
/2) and C2) and placenta. However, the same DNA-protein complex was not det
ected in extracts from liver or liver-derived cell lines (HepG2 and Hep3B).
Taken together, our results demonstrate the presence of a DNA-binding prot
ein, termed tissue-specific repressor, found only in nonhepatocytes which m
ay function to repress SAA1 gene expression by interacting with a repressor
element. Thus, liver-specific expression of the SAA1 gene is apparently re
gulated by both positive and negative regulatory elements and their interac
ting transcription factors to ensure that it is expressed only in suitable
cell types. (C) 1999 Academic Press.