scholarly journals CCAAT enhancer binding protein β and hepatocyte nuclear factor 3β are necessary and sufficient to mediate dexamethasone-induced up-regulation of alpha2HS-glycoprotein/fetuin-A gene expression

2006 ◽  
Vol 36 (2) ◽  
pp. 261-277 ◽  
Author(s):  
Michael Wöltje ◽  
Beate Tschöke ◽  
Verena von Bülow ◽  
Ralf Westenfeld ◽  
Bernd Denecke ◽  
...  
Keyword(s):  
Serum Protein ◽  
Binding Protein ◽  
Protein A ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Tissue Remodelling ◽  
Mobility Shift ◽  
Fetuin A ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein

Alpha2HS-glycoprotein/fetuin-A (Ahsg) is a serum protein preventing soft tissue calcification. In trauma and inflammation, Ahsg is down-regulated and therefore considered a negative acute phase protein. Enhancement of Ahsg expression as a protective serum protein is desirable in several diseases including tissue remodelling after trauma and infection, kidney and heart failure, and cancer. Using reporter gene assays in hepatoma cells combined with electrophoretic mobility shift assays we determined that dexamethasone up-regulates hepatic Ahsg. A steroid response unit at position −146/−119 within the mouse Ahsg promoter mediates the glucocorticoid-induced increase of Ahsg mRNA. It binds the hepatocyte nuclear factor 3β and CCAAT enhancer binding protein β (C/EBP-β). The up-regulation is mediated indirectly via glucocorticoid hormone-induced transcriptional up-regulation in C/EBP-β protein. A high degree of sequence identity in mouse, rat and human Ahsg promoters suggests that the promoter is similarly up-regulated by dexamethasone in all three species. Therefore, our findings suggest that glucocorticoids may be used to enhance the level of Ahsg protein circulating in serum.

scholarly journals A Distal Region Involving Hepatocyte Nuclear Factor 4α and CAAT/Enhancer Binding Protein Markedly Potentiates the Protein Kinase A Stimulation of the Glucose-6-Phosphatase Promoter

2005 ◽  
Vol 19 (1) ◽  
pp. 163-174 ◽  
Author(s):  
Amandine Gautier-Stein ◽  
Gilles Mithieux ◽  
Fabienne Rajas
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Binding Sites ◽  
Binding Protein ◽  
Distal Region ◽  
Proximal Region ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Enhancer Binding Protein ◽  
Kinase A

Abstract Glucose-6-phosphatase (Glc6Pase) is the last enzyme of gluconeogenesis and is only expressed in the liver, kidney, and small intestine. In these tissues, the mRNA and its activity are increased when cAMP levels increased (e.g. in fasting or diabetes). We first report that a proximal region (within −200 bp relative to the transcription start site) and a distal region (−694/−500 bp) are both required for a potent cAMP and a protein kinase A (PKA) responsiveness of the Glc6Pase promoter. Using different molecular approaches, we demonstrate that hepatocyte nuclear factor (HNF4α), CAAT/ enhancer-binding protein-α (C/EBPα), C/EBPβ, and cAMP response element-binding protein (CREB) are involved in the potentiated PKA responsiveness: in the distal region, via one HNF4α- and one C/EBP-binding sites, and in the proximal region, via two HNF4α and two CREB-binding sites. We also show that HNF4α, C/EBPα, and C/EBPβ are constitutively bound to the endogenous Glc6Pase gene, whereas CREB and CREB-binding protein (CBP) will be bound to the gene upon stimulation by cAMP. These data strongly suggest that the cAMP responsiveness of the Glc6Pase promoter requires a tight cooperation between a proximal and a distal region, which depends on the presence of several HNF4α-, C/EBP-, and CREB-binding sites, therefore involving an intricate association of hepatic and ubiquitous transcription factors.

scholarly journals Delta-interacting Protein A, a New Inhibitory Partner of CCAAT/Enhancer-binding Protein β, Implicated in Adipocyte Differentiation

2005 ◽  
Vol 280 (12) ◽  
pp. 11432-11438 ◽  
Author(s):  
Olivier Bezy ◽  
Christian Elabd ◽  
Olivia Cochet ◽  
Rasmus K. Petersen ◽  
Karsten Kristiansen ◽  
...  
Keyword(s):  
Adipocyte Differentiation ◽  
Binding Protein ◽  
Protein A ◽  
Interacting Protein ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein

A novel myeloid-restricted zebrafish CCAAT/enhancer-binding protein with a potent transcriptional activation domain

Blood ◽  
2001 ◽  
Vol 97 (9) ◽  
pp. 2611-2617 ◽  
Author(s):  
Susan E. Lyons ◽  
Bixiong C. Shue ◽  
Andrew C. Oates ◽  
Leonard I. Zon ◽  
P. Paul Liu
Keyword(s):  
Dna Binding ◽  
Transcriptional Activation ◽  
Binding Protein ◽  
Myeloid Cells ◽  
Mobility Shift ◽  
Nih3t3 Cells ◽  
Amino Terminal ◽  
Enhancer Binding Protein ◽  
Bzip Domain ◽  
Ccaat Enhancer Binding Protein

Abstract The CCAAT/enhancer-binding protein (C/EBP) family consists of transcription factors essential for hematopoiesis. The defining feature of the C/EBPs is a highly conserved carboxy-terminal bZIP domain that is necessary and sufficient for dimerization and DNA binding, whereas their amino-terminal domains are unique. This study reports a novelc/ebp gene (c/ebp1) from zebrafish that encodes a protein homologous to mammalian C/EBPs within the bZIP domain, but with an amino terminus lacking homology to any C/EBP or to any known sequence. In zebrafish embryos, c/ebp1 expression was initially observed in cells within the yolk sac circulation valley at approximately the 16-to 18-somite stage, and at 24 hours postfertilization (hpf), also in circulating cells. Mostc/ebp1+cells also expressed a known early macrophage marker, leukocyte-specific plastin (l-plastin). Expression of both markers was lost in cloche, a mutant affecting hematopoiesis at the level of the hemangioblast. Expression of both markers was retained in m683 andspadetail, mutants affecting erythropoiesis, but not myelopoiesis. Further, c/ebp1 expression was lost in a mutant with defective myelopoiesis, but intact erythropoiesis. These data suggest that c/ebp1 is expressed exclusively in myeloid cells. In electrophoretic mobility shift assays, c/ebp1 was able to bind a C/EBP consensus DNA site. Further, a chimeric protein containing the amino-terminal domain of c/ebp1 fused to the DNA-binding domain of GAL4 induced a GAL4 reporter 4000-fold in NIH3T3 cells. These results suggest that c/ebp1 is a novel member of the C/EBP family that may function as a potent transcriptional activator in myeloid cells.

Sign in / Sign up

Export Citation Format

Share Document