Identification of beta-cell-specific insulin gene transcription factor RIPE3b1 as mammalian MafA.

Published

Journal Article

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.

Full Text

Cited Authors

  • Olbrot, M; Rud, J; Moss, LG; Sharma, A

Published Date

  • May 2002

Published In

Volume / Issue

  • 99 / 10

Start / End Page

  • 6737 - 6742

PubMed ID

  • 12011435

Pubmed Central ID

  • 12011435

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.102168499

Language

  • eng