scholarly journals Transcription Factor Hepatocyte Nuclear Factor 6 Regulates Pancreatic Endocrine Cell Differentiation and Controls Expression of the Proendocrine Gene ngn3

2000 ◽  
Vol 20 (12) ◽  
pp. 4445-4454 ◽  
Author(s):  
Patrick Jacquemin ◽  
Serge M. Durviaux ◽  
Jan Jensen ◽  
Catherine Godfraind ◽  
Gerard Gradwohl ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Differentiation ◽  
Endocrine Cell ◽  
Endocrine Cells ◽  
Glucose Transporter ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Mouse Development ◽  
Endocrine Differentiation ◽  
Glucose Transporter 2

ABSTRACT Hepatocyte nuclear factor 6 (HNF-6) is the prototype of a new class of cut homeodomain transcription factors. During mouse development, HNF-6 is expressed in the epithelial cells that are precursors of the exocrine and endocrine pancreatic cells. We have investigated the role of HNF-6 in pancreas differentiation by inactivating its gene in the mouse. In hnf6 −/− embryos, the exocrine pancreas appeared to be normal but endocrine cell differentiation was impaired. The expression of neurogenin 3 (Ngn-3), a transcription factor that is essential for determination of endocrine cell precursors, was almost abolished. Consistent with this, we demonstrated that HNF-6 binds to and stimulates the ngn3 gene promoter. At birth, only a few endocrine cells were found and the islets of Langerhans were missing. Later, the number of endocrine cells increased and islets appeared. However, the architecture of the islets was perturbed, and their β cells were deficient in glucose transporter 2 expression. Adult hnf6 −/− mice were diabetic. Taken together, our data demonstrate that HNF-6 controls pancreatic endocrine differentiation at the precursor stage and identify HNF-6 as the first positive regulator of the proendocrine gene ngn3in the pancreas. They also suggest that HNF-6 is a candidate gene for diabetes mellitus in humans.

scholarly journals Hepatocyte Nuclear Factor 1A Is a Cell-Intrinsic Transcription Factor Required for B Cell Differentiation and Development in Mice

2016 ◽  
Vol 196 (4) ◽  
pp. 1655-1665 ◽  
Author(s):  
Karin von Wnuck Lipinski ◽  
Katherine Sattler ◽  
Susann Peters ◽  
Sarah Weske ◽  
Petra Keul ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Differentiation ◽  
B Cell ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
B Cell Differentiation ◽  
A Cell

S1690 Hepatocyte Nuclear Factor-1alpha is Critical for Gut Endocrine Cell Differentiation

2010 ◽  
Vol 138 (5) ◽  
pp. S-254
Author(s):  
François Brial ◽  
Carine Lussier ◽  
Francois Boudreau
Keyword(s):  
Cell Differentiation ◽  
Endocrine Cell ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor

Mutation P291fsinsC in the transcription factor hepatocyte nuclear factor-1alpha is dominant negative

Diabetes ◽  
1998 ◽  
Vol 47 (8) ◽  
pp. 1231-1235 ◽  
Author(s):  
K. Yamagata ◽  
Q. Yang ◽  
K. Yamamoto ◽  
H. Iwahashi ◽  
J. Miyagawa ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dominant Negative ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor

The restricted promoter activity of the liver transcription factor hepatocyte nuclear factor 3 beta involves a cell-specific factor and positive autoactivation

1992 ◽  
Vol 12 (2) ◽  
pp. 552-562
Author(s):  
L Pani ◽  
X B Quian ◽  
D Clevidence ◽  
R H Costa
Keyword(s):  
Transcription Factor ◽  
Promoter Activity ◽  
Binding Activity ◽  
Specific Factor ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

The transcription factor hepatocyte nuclear factor 3 (HNF-3) is involved in the coordinate expression of several liver genes. HNF-3 DNA binding activity is composed of three different liver proteins which recognize the same DNA site. The HNF-3 proteins (designated alpha, beta, and gamma) possess homology in the DNA binding domain and in several additional regions. To understand the cell-type-specific expression of HNF-3 beta, we have defined the regulatory sequences that elicit hepatoma-specific expression. Promoter activity requires -134 bp of HNF-3 beta proximal sequences and binds four nuclear proteins, including two ubiquitous factors. One of these promoter sites interacts with a novel cell-specific factor, LF-H3 beta, whose binding activity correlates with the HNF-3 beta tissue expression pattern. Furthermore, there is a binding site for the HNF-3 protein within its own promoter, suggesting that an autoactivation mechanism is involved in the establishment of HNF-3 beta expression. We propose that both the LF-H3 beta and HNF-3 sites play an important role in the cell-type-specific expression of the HNF-3 beta transcription factor.

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.

Mutation P291fsinsC in the Transcription Factor Hepatocyte Nuclear Factor-1  is Dominant Negative

Diabetes ◽  
1998 ◽  
Vol 47 (8) ◽  
pp. 1231-1235 ◽  
Author(s):  
K. Yamagata ◽  
Q. Yang ◽  
K. Yamamoto ◽  
H. Iwahashi ◽  
J.-i. Miyagawa ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dominant Negative ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Nuclear Factor 1

scholarly journals Transcriptional regulation of the distal promoter of the rat pyruvate carboxylase gene by hepatocyte nuclear factor 3β/Foxa2 and upstream stimulatory factors in insulinoma cells

2007 ◽  
Vol 405 (2) ◽  
pp. 359-367 ◽  
Author(s):  
Thirajit Boonsaen ◽  
Pinnara Rojvirat ◽  
Kathy H. Surinya ◽  
John C. Wallace ◽  
Sarawut Jitrapakdee
Keyword(s):  
Transcription Factor ◽  
Reporter Gene ◽  
Pyruvate Carboxylase ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Promoter Fragment ◽  
Gel Retardation ◽  
E Box ◽  
Insulinoma Cells ◽  
Distal Promoter

PC (pyruvate carboxylase) plays a crucial role in intermediary metabolism including glucose-induced insulin secretion in pancreatic islets. In the present study, we identified two regions of the 1.2 kb distal promoter, the −803/−795 site and the −408/−403 E-box upstream of the transcription start site, as the important cis-acting elements for transcriptional activation of the luciferase reporter gene. Site-directed mutagenesis of either one of these sites in the context of this 1.2 kb promoter fragment, followed by transient transfections in the insulinoma cell line, INS-1, abolished reporter activity by approx. 50%. However, disruption of either the −803/−795 or the −408/−403 site did not affect reporter gene activity in NIH 3T3 cells, suggesting that this promoter fragment is subjected to cell-specific regulation. The nuclear proteins that bound to these −803/−795 and −408/−403 sites were identified by gel retardation assays as HNF3β (hepatocyte nuclear factor 3β)/Foxa2 (forkhead/winged helix transcription factor box2) and USFs (upstream stimulatory factors), USF1 and USF2, respectively. Chromatin immunoprecipitation assays using antisera against HNF3β/Foxa2, USF1 and USF2 demonstrated that endogenous HNF3β/Foxa2 binds to the −803/−795 Foxa2 site, and USF1 and USF2 bind to the −408/−403 E-box respectively in vivo, consistent with the gel retardation assay results. Although there are weak binding sites located at regions −904 and −572 for PDX1 (pancreatic duodenal homeobox-1), a transcription factor that controls expression of β-cell-specific genes, it did not appear to regulate PC expression in INS-1 cells in the context of the 1.2 kb promoter fragment. The results presented here show that Foxa2 and USFs regulate the distal promoter of the rat PC gene in a cell-specific manner.

scholarly journals Hepatocyte nuclear factor 6, a transcription factor that contains a novel type of homeodomain and a single cut domain.

1996 ◽  
Vol 93 (18) ◽  
pp. 9460-9464 ◽  
Author(s):  
F. P. Lemaigre ◽  
S. M. Durviaux ◽  
O. Truong ◽  
V. J. Lannoy ◽  
J. J. Hsuan ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor
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