Regulation of the pancreatic pro-endocrine gene neurogenin3

Diabetes
J C LeeM S German

Abstract

Neurogenin3 (ngn3), a basic helix-loop-helix (bHLH) transcription factor, functions as a pro-endocrine factor in the developing pancreas: by itself, it is sufficient to force undifferentiated pancreatic epithelial cells to become islet cells. Because ngn3 expression determines which precursor cells will differentiate into islet cells, the signals that regulate ngn3 expression control islet cell formation. To investigate the factors that control ngn3 gene expression, we mapped the human and mouse ngn3 promoters and delineated transcriptionally active sequences within the human promoter. Surprisingly, the human ngn3 promoter drives transcription in all cell lines tested, including fibroblast cell lines. In contrast, in transgenic animals the promoter drives expression specifically in regions of ngn3 expression in the developing pancreas and gut; and the addition of distal sequences greatly enhances transgene expression. Within the distal enhancer, binding sites for several pancreatic transcription factors, including hepatocyte nuclear factor (HNF)-1 and HNF-3, form a tight cluster. HES1, an inhibitory bHLH factor activated by Notch signaling, binds to the proximal promoter and specifically blocks promoter activity. Together with ...Continue Reading

References

Aug 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·L A EmensL G Moss
Nov 27, 1991·Biochemical and Biophysical Research Communications·T NoguchiT Tanaka
May 1, 1994·Molecular and Cellular Biology·J PhilippeV R Prezioso
May 1, 1997·Molecular and Cellular Biology·S SharmaM Montminy
May 1, 1997·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·M Sander, M S German
Nov 14, 1997·The Journal of Biological Chemistry·C Wu
May 29, 1998·The Journal of Clinical Investigation·M PontoglioK S Polonsky
Dec 4, 1998·Diabetes·H Edlund
Jan 20, 1999·Seminars in Cell & Developmental Biology·J Lewis
Apr 30, 1999·Science·S Artavanis-TsakonasR J Lake
Sep 1, 1999·Proceedings of the National Academy of Sciences of the United States of America·D Q ShihM Stoffel
Sep 7, 1999·Nature·A ApelqvistH Edlund
Nov 24, 1999·Mechanisms of Development·C CoffinierM Yaniv
Dec 30, 1999·Nature Genetics·J JensenO D Madsen
Mar 4, 2000·Proceedings of the National Academy of Sciences of the United States of America·G GradwohlF Guillemot

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Citations

Dec 18, 2001·Diabetes/metabolism Research and Reviews·B NazlielB Koçer
Mar 29, 2002·Diabetes/metabolism Research and Reviews·Alberto Pugliese, Donatella Miceli
Nov 10, 2006·Cell and Tissue Research·Camilla KarlssonAnders Lindahl
Apr 12, 2003·Experimental Cell Research·Jean-Philippe CoppéPierre-Yves Desprez
Feb 20, 2003·Trends in Endocrinology and Metabolism : TEM·Swarup K Chakrabarti, Raghavendra G Mirmira
Mar 13, 2012·Nature Genetics·Chutima TalchaiDomenico Accili
Oct 5, 2011·Proceedings of the National Academy of Sciences of the United States of America·Limor LandsmanMatthias Hebrok
Mar 22, 2013·BioResearch Open Access·Ivka AfrikanovaAlberto Hayek
Jun 26, 2007·Nucleic Acids Research·Andreas Fischer, Manfred Gessler
Jun 29, 2006·Pancreas·Nikiforos BallianXiao-Ping Wang
Nov 30, 2012·Journal of the Royal Society, Interface·Walter de BackLutz Brusch
Aug 5, 2008·Genes & Development·Jennifer M Oliver-Krasinski, Doris A Stoffers
Aug 20, 2005·Development, Growth & Differentiation·Shoen Kume
Jan 19, 2010·Development, Growth & Differentiation·Keiichi KatsumotoShoen Kume
Dec 21, 2007·Diabetes, Obesity & Metabolism·J-F LouetF Mauvais-Jarvis
Oct 18, 2008·Diabetes, Obesity & Metabolism·A KhalailehY Dor
Oct 18, 2008·Diabetes, Obesity & Metabolism·L Baeyens, L Bouwens
Aug 17, 2011·Diabetes, Obesity & Metabolism·H J LiA B Leiter
Sep 7, 2012·Diabetes, Obesity & Metabolism·O Dumortier, E Van Obberghen
Sep 16, 2003·Molecular and Cellular Biology·Michel-Olivier GrattonStefano Stifani
Nov 26, 2009·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·R A CoadJ M W Slack
Aug 6, 2013·Annual Review of Cell and Developmental Biology·Hung Ping ShihMaike Sander
Oct 23, 2003·Annual Review of Cell and Developmental Biology·L Charles Murtaugh, Douglas A Melton
Jun 3, 2009·The Journal of Clinical Investigation·Jennifer M Oliver-KrasinskiDoris A Stoffers
May 3, 2013·The Journal of Clinical Investigation·Yoshiya Kawaguchi
Mar 22, 2006·Pediatric Research·Juris J MeierPeter C Butler
Apr 25, 2009·Endocrine Reviews·Tingxia Guo, Matthias Hebrok
Oct 2, 2009·Development·Renaud Desgraz, Pedro L Herrera
Dec 8, 2010·Disease Models & Mechanisms·Yoshinori ShimajiriMichael S German

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