Transcriptional Control of the Human Aldehyde Dehydrogenase 2 Promoter by Hepatocyte Nuclear Factor 4: Inhibition by Cyclic AMP and COUP Transcription Factors

2002 ◽  
Vol 398 (1) ◽  
pp. 79-86 ◽  
Author(s):  
Min You ◽  
Monika Fischer ◽  
Won Kyoo Cho ◽  
David Crabb
Keyword(s):  
Transcription Factors ◽  
Cyclic Amp ◽  
Aldehyde Dehydrogenase ◽  
Transcriptional Control ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Aldehyde Dehydrogenase 2 ◽  
Hepatocyte Nuclear Factor 4

Binding and activation of the human aldehyde dehydrogenase 2 promoter by hepatocyte nuclear factor 4

1998 ◽  
Vol 1399 (2-3) ◽  
pp. 181-186 ◽  
Author(s):  
Mark J. Stewart ◽  
Katrina M. Dipple ◽  
Mats Estonius ◽  
Harikrishna Nakshatri ◽  
Lynn M. Everett ◽  
...  
Keyword(s):  
Aldehyde Dehydrogenase ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Aldehyde Dehydrogenase 2 ◽  
Hepatocyte Nuclear Factor 4

The activation function-1 of hepatocyte nuclear factor-4 is an acidic activator that mediates interactions through bulky hydrophobic residues

2001 ◽  
Vol 356 (2) ◽  
pp. 635-642 ◽  
Author(s):  
Elena KISTANOVA ◽  
Helen DELL ◽  
Panayota TSANTILI ◽  
Eileen FALVEY ◽  
Christos CLADARAS ◽  
...  
Keyword(s):  
Amino Acids ◽  
Transcription Factors ◽  
Binding Protein ◽  
Activation Function ◽  
Transcriptional Analysis ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Hydrophobic Residues ◽  
Charged Residues ◽  
Hepatocyte Nuclear Factor 4

The hepatocyte nuclear factor-4 (HNF-4) contains two transcription activation domains. One domain, activation function-1 (AF-1), consists of the extreme N-terminal 24 amino acids and functions as a constitutive autonomous activator of transcription. This short transactivator belongs to the class of acidic activators, and it is predicted to adopt an amphipathic α-helical structure. Transcriptional analysis of sequential point mutations of the negatively charged residues (Asp and Glu) revealed a stepwise decrease in activity, while mutation of all acidic residues resulted in complete loss of transcriptional activity. Mutations of aromatic and hydrophobic amino acids surrounding the negatively charged residues had a much more profound effect than mutations of acidic amino acids, since even a single mutation of these residues resulted in a dramatic decrease in transactivation, thus demonstrating the importance of hydrophobic residues in AF-1 activity. Like other acidic activators, the AF-1 of HNF-4 binds the transcription factor IIB and the TATA-binding protein directly in vitro. In addition, the cAMP-response-element-binding-protein, a transcriptional adapter involved in the transactivation of a plethora of transcription factors, interacts with the AF-1 of HNF-4 and co-operates in the process of transactivation by HNF-4. The different protein targets of AF-1 suggest that the AF-1 of HNF-4 may be involved in recruiting both general transcription factors and chromatin remodelling proteins during activation of gene expression.

scholarly journals Chicken ovalbumin upstream promoter transcription factors act as auxiliary cofactors for hepatocyte nuclear factor 4 and enhance hepatic gene expression.

1997 ◽  
Vol 17 (5) ◽  
pp. 2790-2797 ◽  
Author(s):  
E Ktistaki ◽  
I Talianidis
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Transcriptional Activation ◽  
Hormone Receptors ◽  
Physical Interaction ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Upstream Promoter ◽  
Hepatocyte Nuclear Factor 4 ◽  
Chicken Ovalbumin

Chicken ovalbumin upstream promoter transcription factors (COUP-TFs) strongly inhibit transcriptional activation mediated by nuclear hormone receptors, including hepatocyte nuclear factor 4 (HNF-4). COUP-TFs repress HNF-4-dependent gene expression by competition with HNF-4 for common binding sites found in several regulatory regions. Here we show that promoters, such as the HNF-1 promoter, which are recognized by HNF-4 but not by COUP-TFs are activated by COUP-TFI and COUP-TFII in conjunction with HNF-4 more than 100-fold above basal levels, as opposed to about 8-fold activation by HNF-4 alone. This enhancement was strictly dependent on an intact HNF-4 E domain. In vitro and in vivo evidence suggests that COUP-TFs enhance HNF-4 activity by a mechanism that involves their physical interaction with the amino acid 227 to 271 region of HNF-4. Our results indicate that in certain promoters, COUP-TFs act as auxiliary cofactors for HNF-4, orienting the HNF-4 activation domain in a more efficient configuration to achieve enhanced transcriptional activity. These findings provide new insights into the regulatory functions of COUP-TFs, suggesting their involvement in the initial activation and subsequent high-level expression of hepatic regulators, as well as in the positive and negative modulation of downstream target genes.

scholarly journals A missense mutation in the hepatocyte nuclear factor 4 alpha gene in a UK pedigree with maturity-onset diabetes of the young

Diabetologia ◽  
1997 ◽  
Vol 40 (7) ◽  
pp. 859-862 ◽  
Author(s):  
M. P. Bulman ◽  
M. J. Dronsfield ◽  
T. Frayling ◽  
M. Appleton ◽  
S. C. Bain ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Nuclear Factor ◽  
Maturity Onset Diabetes ◽  
Hepatocyte Nuclear Factor ◽  
Onset Diabetes ◽  
Hepatocyte Nuclear Factor 4 ◽  
Alpha Gene
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