scholarly journals Upstream region of rat serum albumin gene promoter contributes to promoter activity: presence of functional binding site for hepatocyte nuclear factor-3

1999 ◽  
Vol 338 (2) ◽  
pp. 241-249 ◽  
Author(s):  
Chin-Hui HSIANG ◽  
Norman W. MARTEN ◽  
Daniel S. STRAUS
Keyword(s):  
Serum Albumin ◽  
Hepg2 Cells ◽  
Promoter Activity ◽  
Gene Promoter ◽  
Upstream Region ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Rat Serum ◽  
Albumin Gene ◽  
Rat Serum Albumin

Transcription of the serum albumin gene occurs almost exclusively in the liver and is controlled in part by a strong liver-specific promoter. The upstream region of the serum albumin gene promoter is highly conserved among species and is footprinted in vitro by a number of nuclear proteins. However, the role of the upstream promoter region in regulating transcription and the identity of the transcription factors that bind to this region have not been established. In the present study, deletion analysis of the rat serum albumin promoter in transiently transfected HepG2 cells demonstrated that elimination of the region between -207 and -153 bp caused a two-fold decrease in promoter activity (P< 0.05). Additional analysis of the -207 to -124 bp promoter interval led to the identification of two potential binding sites for hepatocyte nuclear factor-3 (HNF-3) located at -168 to -157 bp (site X) and -145 to -134 bp (site Y). Electrophoretic mobility-shift assays performed with the HNF-3 X and Y sites demonstrated that both sites are capable of binding HNF-3α and HNF-3β. Placement of a single copy of the HNF-3 X site upstream from a minimal promoter increased promoter activity by about four-fold in HepG2 cells, and the reporter construct containing this site could be transactivated if co-transfected with an HNF-3 expression construct. Furthermore, inactivation of the HNF-3 X site by site-directed mutagenesis within the context of the -261 bp albumin promoter construct resulted in a 40% decrease in transcription (P< 0.05). These results indicate that the positive effect of the -207 to -153 bp promoter interval is attributable to the presence of the HNF-3 X site within this interval. Additional results obtained with transfected HepG2 cells suggest that the HNF-3 Y site plays a lesser role in activation of transcription than the X site.

scholarly journals The rat serum albumin gene: analysis of cloned sequences.

1979 ◽  
Vol 76 (7) ◽  
pp. 3256-3260 ◽  
Author(s):  
T. D. Sargent ◽  
J. R. Wu ◽  
J. M. Sala-Trepat ◽  
R. B. Wallace ◽  
A. A. Reyes ◽  
...  
Keyword(s):  
Serum Albumin ◽  
Gene Analysis ◽  
Rat Serum ◽  
Albumin Gene ◽  
Rat Serum Albumin

scholarly journals Fine structure and evolution of the rat serum albumin gene

1981 ◽  
Vol 1 (10) ◽  
pp. 871-883
Author(s):  
T D Sargent ◽  
L L Jagodzinski ◽  
M Yang ◽  
J Bonner
Keyword(s):  
Serum Albumin ◽  
Common Ancestor ◽  
Duplication Event ◽  
Loop Analysis ◽  
Rat Serum ◽  
Messenger Ribonucleic Acid ◽  
Albumin Gene ◽  
Flanking Sequences ◽  
Exon Junctions ◽  
Rat Serum Albumin

The exons, their boundaries, and approximately half of the intronic deoxyribonucleic acid of the rat serum albumin gene were sequenced. In addition to the 14 exons identified earlier by R-loop analysis, a small exon was detected between the "leader" exon (Z) and exon B. The leader exon encoded the 5'-untranslated portion of albumin messenger ribonucleic acid and the "pre-pro" oligopeptide present on the nascent protein. The sites of initiation and termination of transcription were tentatively identified by comparison of the 5' and 3' gene-flanking sequences with those of other eucaryotic genes. All 28 intron/exon junctions conformed to the "GT-AG rule" (Breathnach et al., Proc. Natl. Acad. Sci. 75:4853-4857, 1978). The three homologous domains of albumin were encoded by three subgenes that consisted of four exons each and evolved by intragenic duplication of a common ancestor. The second and forth exons of each subgene appeared to be the result of an even earlier duplication event. We propose a model for the evolution of this gene that accounts for the observed patterns of exon size and homology.

Regulation of kidney-specific Ksp-cadherin gene promoter by hepatocyte nuclear factor-1β

2002 ◽  
Vol 283 (4) ◽  
pp. F839-F851 ◽  
Author(s):  
Yun Bai ◽  
Marco Pontoglio ◽  
Thomas Hiesberger ◽  
Angus M. Sinclair ◽  
Peter Igarashi
Keyword(s):  
Promoter Activity ◽  
Gene Promoter ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Specific Gene ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Tissue Specific ◽  
Transfected Cells

Kidney-specific cadherin (Ksp-cadherin) is a tissue-specific member of the cadherin family that is expressed exclusively in the kidney and developing genitourinary tract. Recent studies have shown that the proximal 250 bp of the Ksp-cadherin gene promoter are sufficient to direct tissue-specific gene expression in vivo and in vitro. The proximal 120 bp of the promoter are evolutionarily conserved between mouse and human and contain a DNase I hypersensitive site that is kidney cell specific. At position −55, the promoter contains a consensus recognition site for hepatocyte nuclear factor-1 (HNF-1). Mutations of the consensus HNF-1 site and downstream GC-boxes inhibit promoter activity in transfected cells. HNF-1α and HNF-1β bind specifically to the −55 site, and both proteins transactivate the promoter directly. Expression of Ksp-cadherin is not altered in the kidneys of HNF-1α-deficient mice. However, expression of a gain-of-function HNF-1β mutant stimulates Ksp-cadherin promoter activity in transfected cells, whereas expression of a dominant-negative mutant inhibits activity. These studies identify Ksp-cadherin as the first kidney-specific promoter that has been shown to be regulated by HNF-1β. Mutations of HNF-1β, as occur in humans with inherited renal cysts and diabetes, may cause dysregulated Ksp-cadherin promoter activity.

scholarly journals Fine structure and evolution of the rat serum albumin gene.

1981 ◽  
Vol 1 (10) ◽  
pp. 871-883 ◽  
Author(s):  
T D Sargent ◽  
L L Jagodzinski ◽  
M Yang ◽  
J Bonner
Keyword(s):  
Serum Albumin ◽  
Common Ancestor ◽  
Duplication Event ◽  
Loop Analysis ◽  
Rat Serum ◽  
Messenger Ribonucleic Acid ◽  
Albumin Gene ◽  
Flanking Sequences ◽  
Exon Junctions ◽  
Rat Serum Albumin

The exons, their boundaries, and approximately half of the intronic deoxyribonucleic acid of the rat serum albumin gene were sequenced. In addition to the 14 exons identified earlier by R-loop analysis, a small exon was detected between the "leader" exon (Z) and exon B. The leader exon encoded the 5'-untranslated portion of albumin messenger ribonucleic acid and the "pre-pro" oligopeptide present on the nascent protein. The sites of initiation and termination of transcription were tentatively identified by comparison of the 5' and 3' gene-flanking sequences with those of other eucaryotic genes. All 28 intron/exon junctions conformed to the "GT-AG rule" (Breathnach et al., Proc. Natl. Acad. Sci. 75:4853-4857, 1978). The three homologous domains of albumin were encoded by three subgenes that consisted of four exons each and evolved by intragenic duplication of a common ancestor. The second and forth exons of each subgene appeared to be the result of an even earlier duplication event. We propose a model for the evolution of this gene that accounts for the observed patterns of exon size and homology.

scholarly journals The Biosynthesis of Rat Serum Albumin

1972 ◽  
Vol 247 (12) ◽  
pp. 3858-3863 ◽  
Author(s):  
Theodore Peters ◽  
James C. Peters
Keyword(s):  
Serum Albumin ◽  
Rat Serum ◽  
Rat Serum Albumin

The restricted promoter activity of the liver transcription factor hepatocyte nuclear factor 3 beta involves a cell-specific factor and positive autoactivation

1992 ◽  
Vol 12 (2) ◽  
pp. 552-562
Author(s):  
L Pani ◽  
X B Quian ◽  
D Clevidence ◽  
R H Costa
Keyword(s):  
Transcription Factor ◽  
Promoter Activity ◽  
Binding Activity ◽  
Specific Factor ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

The transcription factor hepatocyte nuclear factor 3 (HNF-3) is involved in the coordinate expression of several liver genes. HNF-3 DNA binding activity is composed of three different liver proteins which recognize the same DNA site. The HNF-3 proteins (designated alpha, beta, and gamma) possess homology in the DNA binding domain and in several additional regions. To understand the cell-type-specific expression of HNF-3 beta, we have defined the regulatory sequences that elicit hepatoma-specific expression. Promoter activity requires -134 bp of HNF-3 beta proximal sequences and binds four nuclear proteins, including two ubiquitous factors. One of these promoter sites interacts with a novel cell-specific factor, LF-H3 beta, whose binding activity correlates with the HNF-3 beta tissue expression pattern. Furthermore, there is a binding site for the HNF-3 protein within its own promoter, suggesting that an autoactivation mechanism is involved in the establishment of HNF-3 beta expression. We propose that both the LF-H3 beta and HNF-3 sites play an important role in the cell-type-specific expression of the HNF-3 beta transcription factor.

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