scholarly journals Hepatocyte Nuclear Factor 4 alpha 2 Messenger RNA Reprograms Liver‐Enriched Transcription Factors and Functional Proteins in End‐Stage Cirrhotic Human Hepatocytes

2021 ◽  
Author(s):  
Edgar N. Tafaleng ◽  
Amitava Mukherjee ◽  
Aaron Bell ◽  
Kazutoyo Morita ◽  
Jorge Guzman‐Lepe ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Messenger Rna ◽  
Human Hepatocytes ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Hepatocyte Nuclear Factor 4 ◽  
End Stage

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

Tissue-specific regulation of mouse hepatocyte nuclear factor 4 expression

1994 ◽  
Vol 14 (11) ◽  
pp. 7276-7284
Author(s):  
W Zhong ◽  
J Mirkovitch ◽  
J E Darnell
Keyword(s):  
Transcription Factor ◽  
Transgenic Mice ◽  
Transient Transfection ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Distal Enhancer ◽  
Specific Expression ◽  
Tissue Specific ◽  
Hypersensitive Sites ◽  
Hepatocyte Nuclear Factor 4

Hepatocyte nuclear factor 4 (HNF-4) is a liver-enriched transcription factor and a member of the steroid hormone receptor superfamily. HNF-4 is required for the hepatoma-specific expression of HNF-1 alpha, another liver-enriched transcription factor, suggesting the early participation of HNF-4 in development. To prepare for further study of HNF-4 in development, the tissue-specific expression of the mouse HNF-4 gene was studied by analyzing the promoter region for required DNA elements. DNase-hypersensitive sites in the gene in liver and kidney tissues were found in regions both distal and proximal to the RNA start that were absent in tissues in which HNF-4 expression did not occur. By use of reporter constructs in transient-transfection assays and with transgenic mice, a region sufficient to drive liver-specific expression of HNF-4 was identified. While an HNF-1 binding site between bp -98 and -68 played an important role in the hepatoma-specific promoter activity of HNF-4 in transient-transfection assays, it was not sufficient for the liver-specific expression of a reporter gene in transgenic mice. Distal enhancer elements indicated by the presence of DNase I-hypersensitive sites at kb -5.5 and -6.5, while not functional in transient-transfection assays, were required for the correct expression of the mouse HNF-4 gene in animals.

Sign in / Sign up

Export Citation Format

Share Document