scholarly journals Delineation of the insulin-responsive sequence in the rat cytosolic aspartate aminotransferase gene: binding sites for hepatocyte nuclear factor-3 and nuclear factor I

1999 ◽  
Vol 343 (3) ◽  
pp. 687-695 ◽  
Author(s):  
Fadela BEURTON ◽  
Uday BANDYOPADHYAY ◽  
Barbara DIEUMEGARD ◽  
Robert BAROUKI ◽  
Martine AGGERBECK
Keyword(s):  
Aspartate Aminotransferase ◽  
Single Mutation ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Insulin Effect ◽  
Factor I ◽  
Nuclear Factor I ◽  
Responsive Element ◽  
Half Site ◽  
Glucocorticoid Effect

Expression of the rat cytosolic aspartate aminotransferase gene is stimulated by glucocorticoids and repressed by insulin in the liver. The regulation by insulin and part of the glucocorticoid effect are mediated by a distal region in the promoter. A 142 bp fragment (-1844 to -1702) confers hormonal sensitivity to the heterologous thymidine kinase promoter in transient-transfection assays in H4IIEC3 hepatoma cells. Footprinting and gel-shift assays showed that several nuclear proteins bind to this region at conserved CCAAT-enhancer binding protein (C/EBP), activator protein (AP-1) and E-box sequences. Hepatocyte nuclear factor-3α (HNF-3)α and β bind to sequences upstream of a glucocorticoid-responsive element (GRE) half-site as demonstrated by supershift experiments. Nuclear factor I (NFI)-like proteins bind downstream of the GRE half-site. These sites around the GRE motif overlap with five insulin responsive element (IRE) -like sequences (TG/ATTT). The effect of insulin was not prevented by any single mutation in the IRE-like sites. However, mutation of two IRE sites (namely IREc and d) prevented the insulin effect although only marginally affecting the glucocorticoid effect. The results suggest that the effect of insulin is due to a complex interplay of factors requiring the synergistic contribution of at least two sites and underline the contribution of HNF-3 and NFI-like proteins.

scholarly journals Hepatocyte nuclear factor 1 binding element within the promoter of microsomal triglyceride transfer protein (MTTP) gene is crucial for MTTP basal expression and insulin responsiveness

2008 ◽  
Vol 41 (4) ◽  
pp. 229-238 ◽  
Author(s):  
Wo-Shing Au ◽  
Liwei Lu ◽  
Chung-Man Yeung ◽  
Ching-Chiu Liu ◽  
Oscar G Wong ◽  
...  
Keyword(s):  
Insulin Response ◽  
Microsomal Triglyceride Transfer Protein ◽  
Gene Promoter ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Insulin Effect ◽  
Transfer Protein ◽  
Insulin Responsiveness ◽  
Nuclear Factor 1 ◽  
Responsive Element

Insulin inhibits the transcription of the microsomal triglyceride transfer protein (MTTP), which plays a pivotal role in lipoprotein assembly and secretion. Here, we provide evidence that a hepatocyte nuclear factor 1 binding element (HNF1A element) within the MTTP promoter serves as a novel negative insulin-responsive element. Deletion/mutation mapping of the MTTP gene promoter identified a modified HNF1A element that is crucial to the negative insulin effect. Chimeric promoter containing this HNF1A element and minimal TEAD1 promoter also responded negatively toward insulin treatment. Gel shift assay demonstrated that HNF1A but not HNF1B binds to this element. Enforced expression of HNF1A was sufficient to reconstitute the negative insulin responsiveness of MTTP promoter in TM4SF1 myocytes that are HNF1A negative. Furthermore, replacing this element with consensus HNF1A element preserved the negative insulin response, suggesting that negative insulin responsiveness is a generic characteristic of HNF1A element. Given that many genes implicated in diabetes contain HNF1A element, the potential regulation of these genes by insulin via HNF1A element may provide important clues for the manifestation and treatment of diabetic metabolic syndromes.

scholarly journals Regulation of Cyp2a5 transcription in mouse primary hepatocytes: roles of hepatocyte nuclear factor 4 and nuclear factor I

2004 ◽  
Vol 381 (3) ◽  
pp. 887-894 ◽  
Author(s):  
Johanna ULVILA ◽  
Satu ARPIAINEN ◽  
Olavi PELKONEN ◽  
Kaoru AIDA ◽  
Tatsuya SUEYOSHI ◽  
...  
Keyword(s):  
Binding Site ◽  
Proximal Promoter ◽  
Luciferase Reporter ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Primary Hepatocytes ◽  
Double Mutation ◽  
Factor I ◽  
Nuclear Factor I ◽  
Hepatocyte Nuclear Factor 4

The cytochrome P4502a5 (Cyp2a5) gene is expressed principally in liver and olfactory mucosa. In the present study, the transcriptional mechanisms of hepatocyte-specific expression of Cyp2a5 were studied in mouse primary hepatocytes. The Cyp2a5 5′-flanking region −3033 to +10 was cloned in front of a luciferase reporter gene and transfected into hepatocytes. Deletion analysis revealed two major activating promoter regions localized at proximal 271 bp and at a more distal area from −3033 to −2014 bp. The proximal activation region was characterized further by DNase I footprinting, and a single clear footprint was detected in the studied area centred over a sequence similar to the NF-I (nuclear factor I)-binding site. The binding of NF-I was confirmed using an EMSA (electrophoretic mobility-shift assay). A putative HNF-4 (hepatocyte nuclear factor 4)-binding site was localized at the proximal promoter by computer analysis of the sequence, and HNF-4α was shown to interact with the site using an EMSA. The functional significance of HNF-4 and NF-I binding to the Cyp2a5 promoter was evaluated by site-directed mutagenesis of the binding motifs in reporter constructs. Both mutations strongly decreased transcriptional activation by the Cyp2a5 promoter in primary hepatocytes, and double mutation almost completely abolished transcriptional activity. Also, the functionality of the distal activation region was found to be dependent on the intact HNF-4 and NF-I sites at the proximal promoter. In conclusion, these results indicate that HNF-4 and NF-I play major roles in the constitutive regulation of hepatic expression of Cyp2a5.

scholarly journals A nuclear factor I-like activity and a liver-specific repressor govern estrogen-regulated in vitro transcription from the Xenopus laevis vitellogenin B1 promoter.

1989 ◽  
Vol 9 (12) ◽  
pp. 5548-5562 ◽  
Author(s):  
B Corthésy ◽  
J R Cardinaux ◽  
F X Claret ◽  
W Wahli
Keyword(s):  
Transcription Initiation ◽  
Regulatory Element ◽  
In Vitro Transcription ◽  
Initiation Site ◽  
Nuclear Factor ◽  
Factor I ◽  
Estrogen Responsive Element ◽  
Nuclear Factor I ◽  
Responsive Element

A hormone-controlled in vitro transcription system derived from Xenopus liver nuclear extracts was exploited to identify novel cis-acting elements within the vitellogenin gene B1 promoter region. In addition to the already well-documented estrogen-responsive element (ERE), two elements were found within the 140 base pairs upstream of the transcription initiation site. One of them, a negative regulatory element, is responsible for the lack of promoter activity in the absence of the hormone and, as demonstrated by DNA-binding assays, interacts with a liver-specific transcription factor. The second is required in association with the estrogen-responsive element to mediate hormonal induction and is recognized by the Xenopus liver homolog of nuclear factor I.

A nuclear factor I-like activity and a liver-specific repressor govern estrogen-regulated in vitro transcription from the Xenopus laevis vitellogenin B1 promoter

1989 ◽  
Vol 9 (12) ◽  
pp. 5548-5562
Author(s):  
B Corthésy ◽  
J R Cardinaux ◽  
F X Claret ◽  
W Wahli
Keyword(s):  
Transcription Initiation ◽  
Regulatory Element ◽  
In Vitro Transcription ◽  
Initiation Site ◽  
Nuclear Factor ◽  
Factor I ◽  
Estrogen Responsive Element ◽  
Nuclear Factor I ◽  
Responsive Element

A hormone-controlled in vitro transcription system derived from Xenopus liver nuclear extracts was exploited to identify novel cis-acting elements within the vitellogenin gene B1 promoter region. In addition to the already well-documented estrogen-responsive element (ERE), two elements were found within the 140 base pairs upstream of the transcription initiation site. One of them, a negative regulatory element, is responsible for the lack of promoter activity in the absence of the hormone and, as demonstrated by DNA-binding assays, interacts with a liver-specific transcription factor. The second is required in association with the estrogen-responsive element to mediate hormonal induction and is recognized by the Xenopus liver homolog of nuclear factor I.

Studies of nuclear factor I/X (NFIX) mutations causing the Marshall-Smith syndrome (MSS)

2017 ◽  
Author(s):  
Kreepa Kooblall ◽  
Mark Stevenson ◽  
Raoul Hennekam ◽  
Rajesh Thakker
Keyword(s):  
Nuclear Factor ◽  
Factor I ◽  
Nuclear Factor I

scholarly journals Nuclear factor I (NF I) binds to an NF I-type site but not to the CCAAT site in the human alpha-globin gene promoter.

1992 ◽  
Vol 267 (12) ◽  
pp. 8478-8484 ◽  
Author(s):  
H Zorbas ◽  
T Rein ◽  
A Krause ◽  
K Hoffmann ◽  
E.L. Winnacker
Keyword(s):  
Globin Gene ◽  
Gene Promoter ◽  
Nuclear Factor ◽  
Factor I ◽  
Alpha Globin ◽  
Nuclear Factor I ◽  
Type Site

scholarly journals Mesenchymal Nuclear factor I B regulates cell proliferation and epithelial differentiation during lung maturation

2011 ◽  
Vol 354 (2) ◽  
pp. 242-252 ◽  
Author(s):  
Yu-Chih Hsu ◽  
Jason Osinski ◽  
Christine E. Campbell ◽  
E. David Litwack ◽  
Dan Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epithelial Differentiation ◽  
Nuclear Factor ◽  
Lung Maturation ◽  
Factor I ◽  
Nuclear Factor I
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