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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum amyloid A (SAA) is a major acute-phase protein synthesized primarily in the liver. Its expression, very low in normal animals, is increased several hundredfold following acute inflammation. To examine DNA sequences involved in liver-specific expression, 5'-flanking regions of the mouse SAA3 gene were analyzed by transient transfection, band shift, and DNase I protection assays. We found that a 56-bp fragment immediately 5' to the TATA box spanning the region -93 to -38 relative to the transcription start site was sufficient to confer liver cell-specific transcriptional activation onto a heterologous promoter in a dose-dependent and orientation-independent manner. This DNA fragment could form DNA-protein complexes with heat-stable nuclear proteins, and the complexes formed could be specifically competed for by excess oligomers corresponding to the C/EBP- or DBP-binding sites but not by binding sites for three other liver-specific factors, HNF1, HNF3, and HNF4. Footprint analysis using Hep3B nuclear extracts revealed two adjacent footprint regions within this 56-bp fragment, the distal region having at least fivefold-greater affinity than the proximal region. Identical footprint patterns were observed when purified recombinant C/EBP protein was used. These results indicated that binding of C/EBP to this 56-bp fragment plays an important role in vivo in enhancing expression of the mouse SAA3 gene in hepatocytes.
Mol Cell Biol 1990 Dec
PMID:Two adjacent C/EBP-binding sequences that participate in the cell-specific expression of the mouse serum amyloid A3 gene. 224 76

Expression of the avian very-low-density apolipoprotein II (apoVLDLII) gene is completely dependent on estrogen and restricted to the liver. We have identified binding sites for nonhistone nuclear proteins located between -1.96 and -2.61 kilobases. One of these sites, located at -2.6 kilobases (designated site 1), was found to span an MspI site that becomes demethylated between days 7 and 9 of embryogenesis, the stage of development at which competence to express the apoVLDLII gene begins to be acquired. Levels of the factor(s) involved were high at day 7 of embryogenesis, decreased two- to threefold by days 9 to 11, and continued to decline more slowly until hatching. Furthermore, the mobility of the complex formed underwent a well-defined shift between days 11 to 13 embryogenesis. Methylation interference studies showed that modification of the outer guanosines of the MspI site resulted in marked inhibition of the formation of the protein-DNA complex. Competition studies, fractionation of nuclear extracts, and tissue distribution indicated that the factor was not the avian homolog of hepatocyte nuclear factor 1, nuclear factor 1, or CCAAT/enhancer-binding protein (C/EBP). However, site 1 could complete for binding to an oligonucleotide, previously shown to be recognized by C/EBP, in a nonreciprocal fashion. These studies demonstrate that the sequence recognized by the protein includes a C/EBP consensus sequence but that elements in addition to the core enhancer motif are essential for binding.
Mol Cell Biol 1990 Jan
PMID:Developmental regulation of specific protein interactions with an enhancerlike binding site far upstream from the avian very-low-density apolipoprotein II gene. 229

The gene for ornithine transcarbamylase (OTC; EC 2.1.3.3), a urea cycle enzyme, is expressed almost exclusively in the liver and small intestine. To identify DNA elements regulating transcription of the OTC gene in the liver, transient expression analysis was carried out by using hepatoma (HepG2) and nonhepatic (CHO) cell lines. The 1.3-kilobase 5'-flanking region of the rat OTC gene directed expression of the fused chloramphenicol acetyltransferase gene in HepG2 cells much more efficiently than in CHO cells. Analysis of deletion mutants of the 5'-flanking region in HepG2 cells revealed that there are at least one negative and two positive regulatory elements within the about 220-base-pair immediate 5'-flanking region. DNase I footprint analysis showed the presence of factors binding to these regulatory elements in nuclear extracts of rat liver and brain, and footprint profiles at the two positive elements exhibited liver-specific features. Transient expression analysis also revealed the existence of an enhancer region located 11 kilobases upstream of the transcription start site. The OTC enhancer was able to activate both its own and heterologous promoters in HepG2 but not in CHO cells. The enhancer was delimited to an about 230-base-pair region, and footprint analysis of this region revealed four protected areas. Footprint profiles at two of the four areas exhibited liver-specific features, and gel shift competition analysis showed that a factor(s) binding to the two liver-specific sites is related to C/EBP. These results suggest that both liver-specific promoter and enhancer elements regulate expression of the OTC gene through interaction with liver-specific factors binding to these elements.
Mol Cell Biol 1990 Mar
PMID:Promoter and 11-kilobase upstream enhancer elements responsible for hepatoma cell-specific expression of the rat ornithine transcarbamylase gene. 230 62

A sequential pattern of interactions of trans-acting factors in rat liver with the phosphoenolpyruvate carboxykinase promoter during late development was observed. A liver-enriched factor, possibly AF1, interacted with the promoter in fetal liver, whereas a factor with the characteristics of C/EBP bound the promoter after birth with the onset of the gene expression.
Mol Cell Biol 1990 May
PMID:Developmentally regulated interactions of liver nuclear factors with the rat phosphoenolpyruvate carboxykinase promoter. 232 58

The far-upstream mouse albumin enhancer (-10.5 to -8.43 kilobases) has both positive and negative regulatory domains which contribute to the rate and tissue specificity of albumin gene transcription. (R. S. Herbst, N. Friedman, J. E. Darnell, Jr., and L. E. Babiss, Proc. Natl. Acad. Sci. USA 86:1553-1557). In this work, the negative regulatory region has been functionally localized to sequences -8.7 to -8.43 kilobases upstream of the albumin gene cap site. In the absence of the albumin-modulating region (in which there are binding sites for the transcription factor C/EBP), the negative region can suppress a neighboring positive-acting element, thereby interfering with albumin enhancer function. The negative region is also capable of negating the positive action of the heterologous transthyretin enhancer in an orientation-independent fashion. Within this negative-acting region we can detect two DNA-binding sites, both of which are recognized by a protein present in all cell types tested. This DNA-binding activity is not competed for by any of a series of known DNA-binding sites, and hence this new protein is a candidate for a role in suppressing the albumin gene in nonhepatic cells.
Mol Cell Biol 1990 Aug
PMID:The mouse albumin enhancer contains a negative regulatory element that interacts with a novel DNA-binding protein. 237 Aug 57

We used the enhancer-binding protein C/EBP as a model to study the nature and the complexity of interaction of an enhancer-binding protein with its target DNA. We found that bacterially expressed C/EBP binds the hepatitis B virus enhancer at multiple sites in a hierarchic and cooperative manner. At low concentrations, only the E element is occupied, but at higher concentrations, additional sites are filled including a site that binds EP, a crucial enhancer-activating protein. This pattern of C/EBP binding may explain the concentration-dependent effect of C/EBP on enhancer activity.
Mol Cell Biol 1990 Aug
PMID:Hierarchic and cooperative binding of the rat liver nuclear protein C/EBP at the hepatitis B virus enhancer. 237 Aug 72

Among the various factors binding to DNA elements within the mouse albumin promoter, NF-Y is the only one present at identical concentrations in the nuclei of all examined tissues. NF-Y binds to albumin promoter element C, which contains the sequence CCAAT. To determine whether this factor augments in vitro transcription from the albumin promoter, an extensive point-mutation analysis was performed within the promoter element C. In liver extracts, six out of the ten mutations result in a strong inhibition of NF-Y binding and in a concomitant decrease in promoter activity. Two mutations that increase the affinity of the C-element for NF-Y also augment the transcription efficiency from the albumin promoter. A similarly strong correlation of NF-Y-binding with transcription efficiency has also been observed in spleen nuclear extracts. The liver-enriched CCAAT and enhancer binding factor C/EBP also recognizes the C element. In contrast to NF-Y, no correlation between the affinity of mutant C-elements for C/EBP and transcriptional activity could be observed in liver nuclear extracts.
J Mol Biol 1990 Aug 20
PMID:A ubiquitous CCAAT factor is required for efficient in vitro transcription from the mouse albumin promoter. 238 72

We have identified an essential cis element in the proximal promoter region of the rat carbamyl phosphate synthetase I (CPSI) gene that is requisite for promoter activity in liver nuclear extracts. Excess synthetic oligonucleotides specifying this region abolished promoter-dependent in vitro transcription. We show that C/EBP, a nuclear factor enriched in liver but found as well in other tissues, such as gut, fat, and lung, interacts with an inverted repeat, GTTGCAAC, at the core of the essential cis element. In brain, a tissue that did not express CPSI or contain significant levels of C/EBP, a different factor was capable of binding at or near the C/EBP recognition element. Activity of the CPSI promoter in liver nuclear extracts was also dependent on sequences 5' to the C/EBP motif; presumably, factors binding to elements within this upstream region are instrumental in restricting CPSI gene expression to liver and intestinal mucosa.
Mol Cell Biol 1989 Jul
PMID:Activity of the carbamyl phosphate synthetase I promoter in liver nuclear extracts is dependent on a cis-acting C/EBP recognition element. 247 60

Adipocyte differentiation is accompanied by the transcriptional activation of many new genes, including the gene encoding adipocyte P2 (aP2), an intracellular lipid-binding protein. Using specific deletions and point mutations, we have shown that at least two distinct sequence elements in the aP2 promoter contribute to the expression of the chloramphenicol acetyltransferase gene in chimeric constructions transfected into adipose cells. An AP-I site at -120, shown earlier to bind Jun- and Fos-like proteins, serves as a positive regulator of chloramphenicol acetyltransferase gene expression in adipocytes but is specifically silenced by adjacent upstream sequences in preadipocytes. Sequences upstream of the AP-I site at -140 (termed AE-1) can function as an enhancer in both cell types when linked to a viral promoter but can stimulate expression only in fat cells in the intact aP2 promoter. The AE-1 sequence binds an adipocyte protein identical or very closely related to an enhancer-binding protein (C/EBP) that has been previously implicated in the regulation of several liver-specific genes. A functional role for C/EBP in the regulation of the aP2 gene is indicated by the facts that C/EBP mRNA is induced during adipocyte differentiation and the aP2 promoter is transactivated by cotransfection of a C/EBP expression vector into preadipose cells. These results indicate that sequences that bind C/EBP and the Fos-Jun complex play major roles in the expression of the aP2 gene during adipocyte differentiation and demonstrate that C/EBP can directly regulate cellular gene expression.
Mol Cell Biol 1989 Dec
PMID:A direct role for C/EBP and the AP-I-binding site in gene expression linked to adipocyte differentiation. 251 32

DNA-protein interactions involving enhancer and promoter sequences within the U3 regions of several avian retroviral long terminal repeats (LTRs) were studied by DNase I footprinting. The rat CCAAT/enhancer-binding protein, C/EBP, bound to all four viral LTRs examined. The Rous sarcoma virus binding site corresponded closely to the 5' limit of the LTR enhancer; nucleotides -225 to -188 were protected as a pair of adjacent binding domains. The Fujinami sarcoma virus LTR bound C/EBP at a single site at nucleotides -213 to -195. C/EBP also bound to the promoter region of the enhancerless Rous-associated virus-0 LTR at nucleotides -77 to -57. The avian myeloblastosis virus LTR bound C/EBP at three sites: nucleotides -262 to -246, -154 to -134, and -55 to -39. We have previously observed binding of C/EBP to an enhancer in the gag gene of avian retroviruses. A heat-treated nuclear extract from chicken liver bound to all of the same retroviral sequences as did C/EBP. Alignment of the avian retroviral binding sequences with the published binding sites for C/EBP in two CCAAT boxes and in the simian virus 40, polyoma, and murine sarcoma virus enhancers suggested TTGNNGCTAATG as a consensus sequence for binding of C/EBP. When two bases of this consensus sequence were altered by site-specific mutagenesis of the Rous sarcoma virus LTR, binding of the heat-stable chicken protein was eliminated.
Mol Cell Biol 1989 Mar
PMID:Avian retroviral long terminal repeats bind CCAAT/enhancer-binding protein. 272 92


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