Identification of beta-cell-specific insulin gene transcription factor RIPE3b1 as mammalian MafA.
Of the three critical enhancer elements that mediate beta-cell-specific and glucose-responsive expression of the insulin gene, only the identity of the transcription factor binding to the RIPE3b element (RIPE3b1) has remained elusive. Using a biochemical purification approach, we have identified the RIPE3b1 factor as a mammalian homologue of avian MafA/L-Maf (mMafA). The avian MafA is a cell-type determination factor that expressed ectopically can trigger lens differentiation program, but no mammalian homologue of avian MafA has previously been identified. Here, we report cloning of the human mafA (hMafA) and demonstrate that it can specifically bind the insulin enhancer element RIPE3b and activate insulin-gene expression. In addition, mMafA has a very restrictive cellular distribution and is selectively expressed in pancreatic beta but not in alpha cells. We suggest that mMafA has an essential role in the function and differentiation of beta-cells and thus may be associated with the pathophysiological origins of diabetes.
Olbrot
Martin
M
Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Boston, MA 02215, USA.
Rud
Jonathan
J
Moss
Larry G
LG
Sharma
Arun
A
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D006224:Cricetinae; D003459:Crystallins / Q000235:genetics; D004742:Enhancer Elements, Genetic; D015870:Gene Expression; D006367:HeLa Cells; D018398:Homeodomain Proteins; D006801:Humans; D007328:Insulin / Q000235:genetics*; D007515:Islets of Langerhans; D037181:Lectins, C-Type; D051473:Maf Transcription Factors, Large; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000145:classification / Q000378:metabolism*; D011971:Receptors, Immunologic; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000145:classification / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D003459:Crystallins; D018398:Homeodomain Proteins; D007328:Insulin; C113413:KLRG1 protein, human; D037181:Lectins, C-Type; C485159:MAFA protein, human; D051473:Maf Transcription Factors, Large; D011518:Proto-Oncogene Proteins; D011971:Receptors, Immunologic; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein