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MafB

An Activator of the Glucagon Gene Expressed in Developing Islet - and ß-Cells

¹ Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee
² Department of Genetics, St. Jude Children’s Research Hospital, Memphis, Tennessee
³ Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, North Carolina

Address correspondence and reprint requests to Roland Stein, Vanderbilt University School of Medicine, Department of Molecular Physiology and Biophysics, 723 Light Hall, Nashville, TN 37232. E-mail: roland.stein{at}vanderbilt.edu

Key Words: CMV, cytomegalovirus • MOI, multiplicity of infection • PEPCK, phosphoenolpyruvate carboxykinase

The large Maf family of basic leucine-zipper–containing transcription factors are known regulators of key developmental and functional processes in various cell types, including pancreatic islets. Here, we demonstrate that within the adult pancreas, MafB is only expressed in islet -cells and contributes to cell type–specific expression of the glucagon gene through activation of a conserved control element found between nucleotides –77 to –51. MafB was also shown to be expressed in developing - and ß-cells as well as in proliferating hormone-negative cells during pancreatogenesis. In addition, MafB expression is maintained in the insulin⁺ and glucagon⁺ cells remaining in mice lacking either the Pax4 or Pax6 developmental regulators, implicating a potentially early role for MafB in gene regulation during islet cell development. These results indicate that MafB is not only important to islet -cell function but may also be involved in regulating genes required in both endocrine - and ß-cell differentiation.

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