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

ABSTRACT: 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.

SUBMITTER: Cyphert HA 

PROVIDER: S-EPMC6341297 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature