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- Title
Examining How the MAFB Transcription Factor Affects Islet β-Cell Function Postnatally.
- Authors
Cyphert, Holly A.; Walker, Emily M.; Yan Hang; Dhawan, Sangeeta; Haliyur, Rachana; Bonatakis, Lauren; Avrahami, Dana; Brissova, Marcela; Kaestner, Klaus H.; Bhushan, Anil; Powers, Alvin C.; Stein, Roland; Hang, Yan
- Abstract
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 MafB 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 MafB in adult mouse β-cells using MafA 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.
- Subjects
TRANSCRIPTION factors; ISLANDS of Langerhans; DNA methylation; TRYPTOPHAN hydroxylase; MICE
- Publication
Diabetes, 2019, Vol 68, Issue 2, p337
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db18-0903