The ubiquitous transcription factor Oct-1 and the liver-specific factor HNF-1 are both required to activate transcription of a hepatitis B virus promoter.

Abstract

The liver-specific transcription factor HNF-1 activates transcription of several mammalian hepatocytespecific genes. The hepatitis B virus preSl promoter shows hepatocyte specificity, which has been ascribed to binding of HNF-1 to a cognate DNA sequence upstream of the TATA box. We show here that there is an adjacent site that binds the ubiquitous transcription factor Oct-1. Both the Oct-1 and HNF-1 sites are necessary for liver-specific transcription of the preSl promoter, but neither site alone activates transcription. The Oct-1 site is also necessary for activation of the preSl promoter in HeLa cells expressing transfected HNF-1. Our results show that while Oct-l is not restricted to hepatocytes, it nevertheless can play a critical role in the expression of a liver-specific gene.The transcriptional activity of any given gene is governed by the constellation of trans-acting cellular factors that bind to its promoter and other cis-acting DNA elements (reviewed in references 29 and 31). The study of model viral genes, such as the simian virus 40 early gene, has been particularly fruitful in delineating these cis-and trans-acting factors in mammalian cells (reviewed in reference 23). Many of the viral genes studied are relatively non-cell type specific and have been mostly studied in dedifferentiated cells such as HeLa cells, hence, they have mostly given insights into non-cell-type-specific transcription. It is likely that analysis of promoters of viruses which show specific tissue tropism can give similarly useful information on cell-type-specific transcription.Hepatitis B virus (HBV) is a hepatotropic virus with four known promoters, all on one strand of the DNA genome (reviewed in references 5 and 18). The two surface gene promoters are in tandem, approximately 400 bp apart (Fig.

PBX2 and PBX3, new homeobox genes with extensive homology to the human proto-oncogene PBX1.

“…The various Pbx proteins were synthesized in vitro and shown to have migrations in SDS gels corresponding to their respective predicted molecular weights: Pbxla, 46,500; Pbxlb, 38,400; Pbx2, 45,900; Pbx3a, 47,100; and Pbx3b, 38,800 (Fig. 6A) domains (26,27) (14) and U4B small nuclear RNA genes (59) and also in DNA replication (45,48,56 (60) have demonstrated that Oct-i and the liver-specific transcription factor HNF1 were both necessary for liver-specific transcription of the hepatitis B virus pre-Sl promoter.…”

A compilation of composite regulatory elements affecting gene transcription in vertebrates

“…In the case of synergism, the level of transcription activation produced by two factors is higher than the sum of the effects produced by each of these factors alone (81,84,(128)(129)(130)(131) (85,127,128,(135)(136)(137)(138)(139).…”

“…One factor can be tissue-specific, one ubiquitous (66,79,80,85,127,128,129), one inducible, one constitutive (74,93,122,126) or both can be inducible yet activated by different molecular signals (70,133,141,143). The interactions between such elements are exemplified in the compilation, where the functional properties of the complexes are described in the column 'Comments' (see Table 1).…”

Characterization of the minimal elements of the hepatitis B virus large surface antigen promoter

“…These results show that additional HBV sequences are not necessary for HNFl-mediated transcriptional activation from this promoter. A previous report suggested that both the Oct-1 and HNF 1 transcription factors were essential for HNFl-mediated transcriptional activation from the large surface antigen promoter (Zhou & Yen, 1991). However, the results of the clustered point mutation and synthetic promoter transfection analyses indicate that the Oct-1 binding site located between -61 and -54 is not necessary for HNFl-mediated transcriptional activation.…”