A basic-leucine zipper transcription factor, MafA, was recently identified as one of the most important transactivators of insulin gene expression. This protein controls the glucose-regulated and pancreatic beta-cell-specific expression of the insulin gene through a cis-regulatory element called RIPE3b/MARE (Maf-recognition element). Here, we show that MafA expression is restricted to beta-cells of pancreatic islets in vivo and in insulinoma cell lines. We also demonstrate that c-Maf, another member of the Maf family of transcription factors, is expressed in islet alpha-cells and in a glucagonoma cell line (alphaTC1), but not in gamma- and delta-cells. An insulinoma cell line, betaTC6, also expressed c-Maf, albeit at a low level. Chromatin immunoprecipitation assays demonstrated that Maf proteins associate with insulin and glucagon promoters in beta- and alpha-cell lines, respectively. c-Maf protein stimulated glucagon promoter activity in a transient luciferase assay, and activation of the glucagon promoter by c-Maf was more efficient than by the other alpha-cell-enriched transcription factors, Cdx2, Pax6, and Isl-1. Furthermore, inhibition of c-Maf expression in alphaTC1 cells by specific short hairpin RNA resulted in marked reduction of the glucagon promoter activity. Thus, c-Maf and MafA are differentially expressed in alpha- and beta-cells where they regulate glucagon and insulin gene expression, respectively.

This article has been cited by other articles:

				J. M. Oliver-Krasinski and D. A. Stoffers On the origin of the {beta} cell Genes & Dev., August 1, 2008; 22(15): 1998 - 2021. [Abstract] [Full Text] [PDF]

				Y. Gosmain, I. Avril, A. Mamin, and J. Philippe Pax-6 and c-Maf Functionally Interact with the {alpha}-Cell-specific DNA Element G1 in Vivo to Promote Glucagon Gene Expression J. Biol. Chem., November 30, 2007; 282(48): 35024 - 35034. [Abstract] [Full Text] [PDF]

				M. C. Lawrence, K. McGlynn, B. Naziruddin, M. F. Levy, and M. H. Cobb Inaugural Article: Differential regulation of CHOP-10/GADD153 gene expression by MAPK signaling in pancreatic beta-cells PNAS, July 10, 2007; 104(28): 11518 - 11525. [Abstract] [Full Text] [PDF]

				K. Kataoka Multiple Mechanisms and Functions of Maf Transcription Factors in the Regulation of Tissue-Specific Genes J. Biochem., June 1, 2007; 141(6): 775 - 781. [Abstract] [Full Text] [PDF]

				N. L. Vanderford, S. S. Andrali, and S. Ozcan Glucose Induces MafA Expression in Pancreatic Beta Cell Lines via the Hexosamine Biosynthetic Pathway J. Biol. Chem., January 19, 2007; 282(3): 1577 - 1584. [Abstract] [Full Text] [PDF]

				C. W. Hay and K. Docherty Comparative Analysis of Insulin Gene Promoters: Implications for Diabetes Research Diabetes, December 1, 2006; 55(12): 3201 - 3213. [Abstract] [Full Text] [PDF]

				I. Artner, J. Le Lay, Y. Hang, L. Elghazi, J. C. Schisler, E. Henderson, B. Sosa-Pineda, and R. Stein MafB: An Activator of the Glucagon Gene Expressed in Developing Islet {alpha}- and {beta}-Cells Diabetes, February 1, 2006; 55(2): 297 - 304. [Abstract] [Full Text] [PDF]

				M. C. Lawrence, K. McGlynn, B.-H. Park, and M. H. Cobb ERK1/2-dependent Activation of Transcription Factors Required for Acute and Chronic Effects of Glucose on the Insulin Gene Promoter J. Biol. Chem., July 22, 2005; 280(29): 26751 - 26759. [Abstract] [Full Text] [PDF]

				C. Zhang, T. Moriguchi, M. Kajihara, R. Esaki, A. Harada, H. Shimohata, H. Oishi, M. Hamada, N. Morito, K. Hasegawa, et al. MafA Is a Key Regulator of Glucose-Stimulated Insulin Secretion Mol. Cell. Biol., June 15, 2005; 25(12): 4969 - 4976. [Abstract] [Full Text] [PDF]

				H. Kaneto, T.-a. Matsuoka, Y. Nakatani, T. Miyatsuka, M. Matsuhisa, M. Hori, and Y. Yamasaki A Crucial Role of MafA as a Novel Therapeutic Target for Diabetes J. Biol. Chem., April 15, 2005; 280(15): 15047 - 15052. [Abstract] [Full Text] [PDF]

				J. S. Harmon, R. Stein, and R. P. Robertson Oxidative Stress-mediated, Post-translational Loss of MafA Protein as a Contributing Mechanism to Loss of Insulin Gene Expression in Glucotoxic Beta Cells J. Biol. Chem., March 25, 2005; 280(12): 11107 - 11113. [Abstract] [Full Text] [PDF]