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Publication
Examining How the MAFB Transcription Factor Affects Islet ß-Cell Function
Postnatally.
Authors Cyphert HA, Walker EM, Hang Y, Dhawan S, Haliyur R, Bonatakis L, Avrahami D,
Brissova M, Kaestner KH, Bhushan A, Powers AC, Stein R
Submitted By Submitted Externally on 2/22/2019
Status Published
Journal Diabetes
Year 2019
Date Published 2/1/2019
Volume : Pages 68 : 337 - 348
PubMed Reference 30425060
Abstract The sustained expression of the MAFB transcription factor in human islet ß-cells
represents a distinct difference in mice. Moreover, mRNA expression of closely
related and islet ß-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 ß-cell population and that MafB expression is postnatally
restricted in mouse ß-cells by de novo DNA methylation. To gain insight into how
MAFB affects human ß-cells, we developed a mouse model to ectopically express
MafB in adult mouse ß-cells using MafA transcriptional control sequences.
Coexpression of MafB with MafA had no overt impact on mouse ß-cells, suggesting
that the human adult ß-cell MAFA/MAFB heterodimer is functionally equivalent to
the mouse MafA homodimer. However, MafB alone was unable to rescue the islet
ß-cell defects in a mouse mutant lacking MafA in ß-cells. Of note, transgenic
production of MafB in ß-cells elevated tryptophan hydroxylase 1 mRNA production
during pregnancy, which drives the serotonin biosynthesis critical for adaptive
maternal ß-cell responses. Together, these studies provide novel insight into
the role of MAFB in human islet ß-cells.




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