Members of the Forkhead box a (Foxa) transcription factor family are expressed in the liver, pancreatic islets and intestine and both Foxa1 and Foxa2 regulate proglucagon gene transcription. As Foxa proteins exhibit overlapping DNA-binding specificities, we examined the role of Foxa3 [hepatocyte nuclear factor (HNF)-3γ] in control of proglucagon gene expression. Foxa3 was detected by reverse transcriptase PCR in glucagon-producing cell lines and binds to the rat proglucagon gene G2 promoter element in GLUTag enteroendocrine cells. Although Foxa3 increased rat proglucagon promoter activity in BHK fibroblasts, augmentation of Foxa3 expression did not increase proglucagon promoter activity in GLUTag cells. Furthermore, adenoviral Foxa3 expression did not affect endogenous proglucagon gene expression in islet or intestinal endocrine cell lines. Although Foxa3-/- mice exhibit mild hypoglycaemia during a prolonged fast, the levels of proglucagon-derived peptides and proglucagon mRNA transcripts were comparable in tissues from wild-type and Foxa3-/- mice. These findings identify Foxa3 as a member of the proglucagon gene G2 element binding-protein family that, unlike Foxa1, is not essential for control of islet or intestinal proglucagon gene expression in vivo.
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September 2002
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Research Article|
September 01 2002
Foxa3 (HNF-3γ) binds to and activates the rat proglucagon gene promoter but is not essential for proglucagon gene expression
Yuanfang LIU;
Yuanfang LIU
∗Department of Medicine, Banting and Best Diabetes Centre, Toronto General Hospital, University of Toronto, 101 College Street CCRW3-845, Toronto, Canada M5G 2C4
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Wei SHEN;
Wei SHEN
†Department of Genetics, University of Pennsylvania, Philadelphia, PA, U.S.A.,
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Patricia L. BRUBAKER;
Patricia L. BRUBAKER
∗Department of Medicine, Banting and Best Diabetes Centre, Toronto General Hospital, University of Toronto, 101 College Street CCRW3-845, Toronto, Canada M5G 2C4
‡Department of Physiology, University of Toronto, 101 College Street CCRW3-845, Toronto, Canada M5G 2C4
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Klaus H. KAESTNER;
Klaus H. KAESTNER
†Department of Genetics, University of Pennsylvania, Philadelphia, PA, U.S.A.,
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Daniel J. DRUCKER
Daniel J. DRUCKER
1
∗Department of Medicine, Banting and Best Diabetes Centre, Toronto General Hospital, University of Toronto, 101 College Street CCRW3-845, Toronto, Canada M5G 2C4
1To whom correspondence should be addressed (e-mail d.drucker@utoronto.ca).
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Publisher: Portland Press Ltd
Received:
January 16 2002
Revision Received:
April 19 2002
Accepted:
May 09 2002
Accepted Manuscript online:
May 09 2002
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2002
2002
Biochem J (2002) 366 (2): 633–641.
Article history
Received:
January 16 2002
Revision Received:
April 19 2002
Accepted:
May 09 2002
Accepted Manuscript online:
May 09 2002
Citation
Yuanfang LIU, Wei SHEN, Patricia L. BRUBAKER, Klaus H. KAESTNER, Daniel J. DRUCKER; Foxa3 (HNF-3γ) binds to and activates the rat proglucagon gene promoter but is not essential for proglucagon gene expression. Biochem J 1 September 2002; 366 (2): 633–641. doi: https://doi.org/10.1042/bj20020095
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