Abstract
We have studied the liver-specific transcriptional activity of the human transferrin gene promoter. Results of competition experiments, site-directed mutagenesis, and 5' deletion analysis have demonstrated that a TATA box and a binding site for the liver-specific protein Tf-LF1 are the only elements needed to direct hepatic-specific transcription in vitro. Thus, Tf-LF1 behaves as other previously described proteins, HNF-1, DBP and LF-A1, in that it is sufficient to confer liver-specific transcriptional activity to a promoter in vitro. This results contrast with observations made in transient expression experiments, in which Tf-LF1 binding alone cannot direct hepatic-specific expression, and the binding of at least one more protein, similar to C/EBP, is needed. Thus, as described for other hepatic genes, the number of elements necessary to confer tissue specificity is different in vivo and in vitro.
MeSH Terms
Base Sequence
Binding Sites
Binding, Competitive
Genes
Humans
Liver/metabolism
Molecular Sequence Data
Mutagenesis, Site-Directed
Organ Specificity/genetics
Promoter Regions, Genetic
TATA Box
Transcription Factors/metabolism
Transcription, Genetic
Transferrin/genetics
Chemicals
Transcription Factors
Transferrin
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Mendelzon D
Laboratoire d'Expression des Gènes Eucaryotes, Institut Pasteur, Paris, France.
Boissier F
Zakin M M
References (18)
18 references, click to expand
-
Factors involved in specific transcription by human RNA polymerase II: analysis by a rapid and quantitative in vitro assay.
Proc Natl Acad Sci U S A. 1985 Jul;82(13):4394-8
PMID: 3925456
-
Expression from the transferrin gene promoter in transgenic mice.
Mol Cell Biol. 1989 Nov;9(11):5154-62
PMID: 2601714
-
Cis- and trans-acting elements responsible for the cell-specific expression of the human alpha 1-antitrypsin gene.
EMBO J. 1987 Sep;6(9):2759-66
PMID: 2824193
-
An albumin enhancer located 10 kb upstream functions along with its promoter to direct efficient, liver-specific expression in transgenic mice.
Genes Dev. 1987 May;1(3):268-76
PMID: 3678824
-
The interplay of DNA-binding proteins on the promoter of the mouse albumin gene.
Cell. 1987 Dec 24;51(6):963-73
PMID: 3690666
-
Tissue-specificity of liver gene expression: a common liver-specific promoter element.
Nucleic Acids Res. 1988 Apr 25;16(8):3165-74
PMID: 2453838
-
Interactions of DNA-binding proteins with the 5' region of the human transferrin gene.
J Biol Chem. 1988 Jul 25;263(21):10180-5
PMID: 2839477
-
Two different liver-specific factors stimulate in vitro transcription from the human alpha 1-antitrypsin promoter.
EMBO J. 1988 Jul;7(7):2075-87
PMID: 3262058
-
A liver-specific factor essential for albumin transcription differs between differentiated and dedifferentiated rat hepatoma cells.
Genes Dev. 1988 Aug;2(8):957-74
PMID: 3169549
-
Multiple hepatic trans-acting factors are required for in vitro transcription of the human alpha-1-antitrypsin gene.
Mol Cell Biol. 1988 Oct;8(10):4362-9
PMID: 3263567
-
Different liver nuclear proteins binds to similar DNA sequences in the 5' flanking regions of three hepatic genes.
Nucleic Acids Res. 1989 Jan 11;17(1):119-33
PMID: 2911463
-
Liver cell specific gene transcription in vitro: the promoter elements HP1 and TATA box are necessary and sufficient to generate a liver-specific promoter.
Nucleic Acids Res. 1989 Feb 11;17(3):939-53
PMID: 2922278
-
Cell type-specific expression of the human transferrin gene. Role of promoter, negative, and enhancer elements.
J Biol Chem. 1989 May 5;264(13):7153-60
PMID: 2708361
-
The role of cis-acting promoter elements in tissue-specific albumin gene expression.
Science. 1989 Apr 21;244(4902):343-6
PMID: 2711183
-
Tissue-specific transcription of the mouse alpha-fetoprotein gene promoter is dependent on HNF-1.
Mol Cell Biol. 1989 Oct;9(10):4204-12
PMID: 2479822
-
Analysis by cell-free transcription of the liver-specific pyruvate kinase gene promoter.
Mol Cell Biol. 1989 Oct;9(10):4409-15
PMID: 2586516
-
The rat albumin promoter: cooperation with upstream elements is required when binding of APF/HNF1 to the proximal element is partially impaired by mutation or bacterial methylation.
Mol Cell Biol. 1989 Nov;9(11):4759-66
PMID: 2689864
-
Interaction of a liver-specific nuclear factor with the fibrinogen and alpha 1-antitrypsin promoters.
Science. 1987 Oct 30;238(4827):688-92
PMID: 3499668