MafB: an activator of the glucagon gene expressed in developing islet alpha- and beta-cells.
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 alpha-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 alpha- and beta-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 alpha-cell function but may also be involved in regulating genes required in both endocrine alpha- and beta-cell differentiation.
Artner
Isabella
I
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Le Lay
John
J
Hang
Yan
Y
Elghazi
Lynda
L
Schisler
Jonathan C
JC
Henderson
Eva
E
Sosa-Pineda
Beatriz
B
Stein
Roland
R
D000818:Animals; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D005934:Glucagon / Q000235:genetics* / Q000378:metabolism; D050416:Glucagon-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D051258:MafB Transcription Factor / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism
D005136:Eye Proteins; D018398:Homeodomain Proteins; D051258:MafB Transcription Factor; C490406:Mafb protein, mouse; D015513:Oncogene Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C110218:Pax4 protein, mouse; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D005934:Glucagon