Pseudopregnancy induces the expression of hepatocyte nuclear factor-1β and its target gene aminopeptidase N in rabbit endometrium via the epithelial promoter

Overexpression of Myc in cells can suppress the transcription of specific genes. Because several of these genes have common transcriptional regulatory elements, we investigated the possibility that this effect of Myc is mediated through a specific transcription factor. In vitro DNA-binding assays detect only one form of CCAAT transcription factor/nuclear factor 1 (CTF/NF-1) in quiescent 3T3-L1 cells. By contrast, quiescent 3T3-L1 cells that stably overexpress either c-Myc or N-Myc contain at least three forms of CTF/NF-1. Biochemical characterization of the various CTF/NF-1 forms showed that they have the same native molecular weight but differ in charge density. The more negatively charged CTF/NF-1 forms present in Myc-overexpressing cells are converted into that found in normal cells by treatment with acid phosphatase, suggesting that they represent a more phosphorylated form of the CTF/NF-1 protein. The various CTF/NF-1 forms have a similar DNA-binding affinity. Transfection experiments demonstrated that transcription from CTF/NF-1-dependent promoters is specifically suppressed in cells that stably overexpress c-Myc. This effect requires CTF/NF-1 binding. CTF/NF-1-dependent promoter activity is also suppressed in 3T3-L1 cells during active growth (relative to the quiescent state). Interestingly, actively growing 3T3-L1 cells contain forms of CTF/NF-1 similar to those in quiescent cells that stably overexpress c-Myc. Thus, the CTF/NF-1 forms present in cells that express high amounts of c-Myc correlate with a lower transcription rate of CTF/NF-1-dependent promoters in vivo. Our results provide a basis for the suppression of specific gene transcription by c-Myc.

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Overexpression of Myc suppresses CCAAT transcription factor/nuclear factor 1-dependent promoters in vivo.

Molecular and Cellular Biology ◽

10.1128/mcb.13.5.3093 ◽

1993 ◽

Vol 13 (5) ◽

pp. 3093-3102 ◽

Cited By ~ 45

Author(s):

B S Yang ◽

J D Gilbert ◽

S O Freytag

Keyword(s):

Transcription Factor ◽

Dna Binding ◽

Regulatory Elements ◽

Specific Gene ◽

Quiescent State ◽

Nuclear Factor ◽

Nuclear Factor 1 ◽

Transcription Factor Nuclear Factor ◽

In Cells

Overexpression of Myc in cells can suppress the transcription of specific genes. Because several of these genes have common transcriptional regulatory elements, we investigated the possibility that this effect of Myc is mediated through a specific transcription factor. In vitro DNA-binding assays detect only one form of CCAAT transcription factor/nuclear factor 1 (CTF/NF-1) in quiescent 3T3-L1 cells. By contrast, quiescent 3T3-L1 cells that stably overexpress either c-Myc or N-Myc contain at least three forms of CTF/NF-1. Biochemical characterization of the various CTF/NF-1 forms showed that they have the same native molecular weight but differ in charge density. The more negatively charged CTF/NF-1 forms present in Myc-overexpressing cells are converted into that found in normal cells by treatment with acid phosphatase, suggesting that they represent a more phosphorylated form of the CTF/NF-1 protein. The various CTF/NF-1 forms have a similar DNA-binding affinity. Transfection experiments demonstrated that transcription from CTF/NF-1-dependent promoters is specifically suppressed in cells that stably overexpress c-Myc. This effect requires CTF/NF-1 binding. CTF/NF-1-dependent promoter activity is also suppressed in 3T3-L1 cells during active growth (relative to the quiescent state). Interestingly, actively growing 3T3-L1 cells contain forms of CTF/NF-1 similar to those in quiescent cells that stably overexpress c-Myc. Thus, the CTF/NF-1 forms present in cells that express high amounts of c-Myc correlate with a lower transcription rate of CTF/NF-1-dependent promoters in vivo. Our results provide a basis for the suppression of specific gene transcription by c-Myc.

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Synergistic activation of the Atlantic salmon hepatocyte nuclear factor (HNF) 1 promoter by the orphan nuclear receptors HNF4 and chicken ovalbumin upstream promoter transcription factor I (COUP-TFI)

Biochemical Journal ◽

10.1042/bj3520557 ◽

2000 ◽

Vol 352 (2) ◽

pp. 557-564 ◽

Cited By ~ 2

Author(s):

Alan MCNAIR ◽

Silvia CEREGHINI ◽

Heike BRAND ◽

Terry SMITH ◽

Christelle BREILLAT ◽

...

Keyword(s):

Transcription Factor ◽

Atlantic Salmon ◽

Nuclear Receptors ◽

Nuclear Hormone Receptor ◽

Nuclear Factor ◽

Hepatocyte Nuclear Factor ◽

Orphan Nuclear Receptors ◽

Synergistic Activation ◽

Upstream Promoter ◽

Chicken Ovalbumin

Hepatocyte nuclear factor 1 (HNF1) is a liver-enriched transcription factor that plays an important role in transcriptional networks involved in liver function. The promoters of mammalian HNF1 genes contains a single binding site for another liver-enriched transcription factor, the nuclear hormone receptor HNF4. A transcriptional hierarchy involving HNF4-mediated activation of the HNF1 promoter has been proposed to be of crucial importance in maintaining the differentiated hepatocyte phenotype. Here we present evidence that the Atlantic salmon HNF1 promoter contains three nuclear-hormone-receptor-binding sequences. Gel-shift assays showed that these motifs are recognized with different affinities by HNF4 and the orphan nuclear receptors chicken ovalbumin upstream promoter transcription factors COUP-TFI and COUP-TFII. In hepatoma cells, the site showing highest affinity for HNF4 appears to be crucial for promoter activity. Transfection experiments in non-hepatic cells indicated that the salmon HNF1 promoter was activated by both HNF4 and COUP-TFs. We also identified a promoter fragment encompassing the two more distal nuclear-hormone-binding sites that was activated by HNF4, unaffected by COUP-TF and showed a strong synergistic activation by HNF4/COUP-TF. Results are presented detailing these interactions in relation to the salmon HNF1 promoter architecture.

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Hepatocyte Nuclear Factor 1, a Transcription Factor at the Crossroads of Glucose Homeostasis

Journal of the American Society of Nephrology ◽

10.1681/asn.v11suppl_2s140 ◽

2000 ◽

Vol 11 (suppl 2) ◽

pp. S140-S143

Author(s):

MARCO PONTOGLIO

Keyword(s):

Transcription Factor ◽

Glucose Homeostasis ◽

Phenylalanine Hydroxylase ◽

Large Set ◽

Nuclear Factor ◽

Hepatocyte Nuclear Factor ◽

Expression Of Genes ◽

Proximal Tubular ◽

Renal Proximal Tubular ◽

Nuclear Factor 1

Abstract. Hepatocyte nuclear factor 1 (HNF1) is a transcription factor involved in the regulation of a large set of hepatic genes, including albumin, β-fibrinogen, and α1-antitrypsin. HNF1 is expressed in the liver, digestive tract, pancreas, and kidney. Mice lacking HNF1 exhibit hepatic, pancreatic, and renal dysfunctions. HNF1-deficient mice fail to express the hepatic phenylalanine hydroxylase gene, giving rise to hyperphenylalaninemia. Renal proximal tubular reabsorption of glucose, phosphate, arginine, and other metabolites is affected, producing severe renal glucosuria, phosphaturia, and amino aciduria. Homozygous mutant mice also exhibit a dramatic insulin secretion defect. This dysfunction resembles that exhibited by patients with maturity-onset diabetes mellitus of the young type 3, who carry mutations in the human HNF1 gene in the heterozygous state. These data show that HNF1 is a major regulator of glucose homeostasis, regulating the expression of genes that are expressed in the liver, kidney, and pancreas.

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Regulation of Hepatocyte Nuclear Factor 1 Activity by Wild-Type and Mutant Hepatitis B Virus X Proteins

Journal of Virology ◽

10.1128/jvi.76.12.5875-5881.2002 ◽

2002 ◽

Vol 76 (12) ◽

pp. 5875-5881 ◽

Cited By ~ 27

Author(s):

Jie Li ◽

Zhenming Xu ◽

Yanyan Zheng ◽

Deborah L. Johnson ◽

Jing-hsiung Ou

Keyword(s):

Transcription Factor ◽

Dna Binding ◽

Binding Site ◽

Core Promoter ◽

Nuclear Factor ◽

Hepatocyte Nuclear Factor ◽

X Protein ◽

The Core ◽

B Virus ◽

Nuclear Factor 1

ABSTRACT The hepatitis B virus (HBV) core promoter regulates the transcription of two related RNA products named precore RNA and core RNA. Previous studies indicate that a double-nucleotide mutation that occurs frequently during chronic HBV infection converts a nuclear receptor binding site in the core promoter to the binding site of the transcription factor hepatocyte nuclear factor-1 (HNF-1) and specifically suppresses the transcription of the precore RNA. This mutation also changes two codons in the overlapping X protein coding sequence. In this report, we demonstrate that the X protein and its mutant Xmt can physically bind to HNF-1 both in vitro and in vivo. Further analyses indicate that both X and Xmt can enhance the gene transactivation and the DNA binding activities of HNF-1. This finding demonstrates for the first time that the X protein can stimulate the DNA binding activity of a homeodomain transcription factor. Interestingly, while both X and Xmt can stimulate the HNF-1 activities, they differ in their effects: a smaller amount of Xmt is needed to generate greater transactivation and DNA binding activities of HNF-1. This functional difference between X and Xmt may have important implications in HBV pathogenesis and is apparently why they have different effects on the core promoter bearing the HNF-1 binding site.

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