scholarly journals Messenger RNA Transcripts of the Hepatocyte Nuclear Factor-1  Gene Containing Premature Termination Codons Are Subject to Nonsense-Mediated Decay

Diabetes ◽  
2004 ◽  
Vol 53 (2) ◽  
pp. 500-504 ◽  
Author(s):  
L. W. Harries ◽  
A. T. Hattersley ◽  
S. Ellard
Keyword(s):  
Messenger Rna ◽  
Premature Termination ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Nonsense Mediated Decay ◽  
Rna Transcripts ◽  
Premature Termination Codons ◽  
Nuclear Factor 1

scholarly journals Premature termination codons in theDMDgene cause reduced local mRNA synthesis

2020 ◽  
Vol 117 (28) ◽  
pp. 16456-16464 ◽  
Author(s):  
Raquel García-Rodríguez ◽  
Monika Hiller ◽  
Laura Jiménez-Gracia ◽  
Zarah van der Pal ◽  
Judit Balog ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Premature Termination ◽  
Epigenetic Mechanism ◽  
Nuclear Compartment ◽  
Transcript Levels ◽  
Nonsense Mediated Decay ◽  
Premature Termination Codons ◽  
Deacetylase Inhibitor ◽  
Repressive Histone Mark

Duchenne muscular dystrophy (DMD) is caused by mutations in theDMDgene leading to the presence of premature termination codons (PTC). Previous transcriptional studies have shown reduced DMD transcript levels in DMD patient and animal model muscles when PTC are present. Nonsense-mediated decay (NMD) has been suggested to be responsible for the observed reduction, but there is no experimental evidence supporting this claim. In this study, we aimed to investigate the mechanism responsible for the drop inDMDexpression levels in the presence of PTC. We observed that the inhibition of NMD does not normalizeDMDgene expression in DMD. Additionally, in situ hybridization showed that DMD messenger RNA primarily localizes in the nuclear compartment, confirming that a cytoplasmic mechanism like NMD indeed cannot be responsible for the observed reduction. Sequencing of nascent RNA to exploreDMDtranscription dynamics revealed a lower rate ofDMDtranscription in patient-derived myotubes compared to healthy controls, suggesting a transcriptional mechanism involved in reduced DMD transcript levels. Chromatin immunoprecipitation in muscle showed increased levels of the repressive histone mark H3K9me3 inmdxmice compared to wild-type mice, indicating a chromatin conformation less prone to transcription inmdxmice. In line with this finding, treatment with the histone deacetylase inhibitor givinostat caused a significant increase in DMD transcript expression inmdxmice. Overall, our findings show that transcription dynamics across theDMDlocus are affected by the presence of PTC, hinting at a possible epigenetic mechanism responsible for this process.

The human beta fibrinogen promoter contains a hepatocyte nuclear factor 1-dependent interleukin-6-responsive element

1993 ◽  
Vol 13 (2) ◽  
pp. 1183-1193
Author(s):  
J Dalmon ◽  
M Laurent ◽  
G Courtois
Keyword(s):  
Binding Site ◽  
Acute Phase ◽  
Interleukin 6 ◽  
Constitutive Expression ◽  
Nuclear Proteins ◽  
Functional Coupling ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Tissue Specific ◽  
Nuclear Factor 1

Acute-phase reactants are liver proteins whose synthesis is positively or negatively regulated during inflammation. The main mediators of this phenomenon are glucocorticoids and interleukin-6 (IL-6), a pleiotropic cytokine that also controls hematopoiesis. Functional analysis of several acute-phase reactant promoter regions has identified two major DNA motifs used by IL-6-regulated genes. The first one corresponds to a CTGG(G/A)AA sequence, and the other is a binding site for members of the C/EBP family of nuclear proteins. We have previously shown that the human beta fibrinogen (beta Fg) promoter contains an IL-6-responsive region, located between bp -150 and -67 (P. Huber, M. Laurent, and J. Dalmon, J. Biol. Chem. 265:5695-5701, 1990). In this study, using DNase I footprinting, mobility shift assays, and mutagenesis, we demonstrate that at least three subdomains of this region are necessary to observe a full response to IL-6. The most distal contains a CTGGGAA motif, and its mutation inhibits IL-6 stimulation. Another, which is able to interact with several distinct nuclear proteins, among them members of the C/EBP family, is dispensable for IL-6 induction but plays an important role in the constitutive expression of beta Fg. Finally, a proximal hepatocyte nuclear factor 1 binding site, already described as the major determinant of beta Fg tissue-specific expression, is also required for IL-6 stimulation. These results indicate a complex interplay between nuclear proteins within the beta Fg IL-6-responsive region and suggest a tight functional coupling between the tissue-specific and inducible elements.

scholarly journals Hepatitis C Virus Infection Suppresses GLUT2 Gene Expression via Downregulation of Hepatocyte Nuclear Factor 1 

2012 ◽  
Vol 86 (23) ◽  
pp. 12903-12911 ◽  
Author(s):  
C. Matsui ◽  
I. Shoji ◽  
S. Kaneda ◽  
I. R. Sianipar ◽  
L. Deng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Hepatitis C Virus Infection ◽  
Glut2 Gene ◽  
Nuclear Factor 1
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