Two distinct factors interact with the promoter regions of several liver-specific genes.
A segment of the human alpha 1-antitrypsin (alpha 1AT) 5'-flanking region comprising nucleotides -137 to -37 from the start of transcription is sufficient to drive liver-specific transcription from the homologous alpha 1AT promoter and from the heterologous SV40 promoter. In this paper we characterize two proteins, LF-A1 and LF-B1, whose ability to bind wild-type and mutant alpha 1AT promoter segments correlates with the ability of these segments to activate transcription in vivo. DNase I protection and methylation interference analysis reveals that LF-A1 recognizes sequences present in the regulatory region of the human alpha 1-antitrypsin, apolipoprotein A1 and haptoglobin-related genes. These sequences share a common 5' TGG/A A/C CC 3' motif. LF-B1 binds to the palindrome 5' TGGTTAAT/ATTCACCA 3' which is present in the human alpha 1-antitrypsin gene between positions -78 and -62 from the start of transcription. LF-B1 also recognizes a related sequence present in the human albumin gene between -66 and -50. These results suggest that LF-A1 and LF-B1 are common positive trans-acting factors which are required for the expression of several genes in the hepatocyte.
Hardon
E M
EM
European Molecular Biology Laboratory, Heidelberg, FRG.
Frain
M
M
Paonessa
G
G
Cortese
R
R
D000418:Albumins / Q000235:genetics; D000818:Animals; D016632:Apolipoprotein A-I; D001054:Apolipoproteins A / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D004790:Enzyme Induction; D005786:Gene Expression Regulation; D005814:Genes, Viral; D006242:Haptoglobins / Q000235:genetics; D006801:Humans; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D012689:Sequence Homology, Nucleic Acid; D013539:Simian virus 40 / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D000515:alpha 1-Antitrypsin / Q000096:biosynthesis / Q000235:genetics*
D000418:Albumins; D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D006242:Haptoglobins; D014157:Transcription Factors; D000515:alpha 1-Antitrypsin