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

Cyphert HA, Walker EM, Hang Y, Dhawan S, Haliyur R, Bonatakis L, Avrahami D, Brissova M, Kaestner KH, Bhushan A, Powers AC, Stein R
Diabetes. 2019 68 (2): 337-348

PMID: 30425060 · PMCID: PMC6341297 · DOI:10.2337/db18-0903

The sustained expression of the MAFB transcription factor in human islet β-cells represents a distinct difference in mice. Moreover, mRNA expression of closely related and islet β-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 β-cell population and that expression is postnatally restricted in mouse β-cells by de novo DNA methylation. To gain insight into how MAFB affects human β-cells, we developed a mouse model to ectopically express in adult mouse β-cells using transcriptional control sequences. Coexpression of MafB with MafA had no overt impact on mouse β-cells, suggesting that the human adult β-cell MAFA/MAFB heterodimer is functionally equivalent to the mouse MafA homodimer. However, MafB alone was unable to rescue the islet β-cell defects in a mouse mutant lacking MafA in β-cells. Of note, transgenic production of MafB in β-cells elevated tryptophan hydroxylase 1 mRNA production during pregnancy, which drives the serotonin biosynthesis critical for adaptive maternal β-cell responses. Together, these studies provide novel insight into the role of MAFB in human islet β-cells.

© 2018 by the American Diabetes Association.

MeSH Terms (15)

Animals Cells, Cultured Chromatin Immunoprecipitation Chromosomes, Artificial, Bacterial DNA Methylation Female Humans Insulin-Secreting Cells In Vitro Techniques MafB Transcription Factor Maf Transcription Factors, Large Mice Mice, Transgenic Pregnancy Tryptophan Hydroxylase

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