Examining How the MAFB Transcription Factor Affects Islet -Cell Function Postnatally

The sustained expression of the MAFB transcription factor in human islet -cells represents a distinct difference in mice. Moreover, mRNA expression of closely related and islet -cell-enriched MAFA does not peak in humans until after 9 years of age. We show that the MAFA protein also is weakly produced within the juvenile human islet -cell population and that MafB expression is postnatally restricted in mouse -cells by de novo DNA methylation. To gain insight into how MAFB affects human -cells, we developed a mouse model to ectopically express MafB in adult mouse -cells using MafA transcriptional control sequences. Coexpression of MafB with MafA had no overt impact on mouse -cells, suggesting that the human adult -cell MAFA/MAFB heterodimer is functionally equivalent to the mouse MafA homodimer. However, MafB alone was unable to rescue the islet -cell defects in a mouse mutant lacking MafA in -cells. Of note, transgenic production of MafB in -cells elevated tryptophan hydroxylase 1 mRNA production during pregnancy, which drives the serotonin biosynthesis critical for adaptive maternal -cell responses. Together, these studies provide novel insight into the role of MAFB in human islet -cells.