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

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.

journal_name

Diabetes

journal_title

Diabetes

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

doi

10.2337/db18-0903

subject

Has Abstract

pub_date

2019-02-01 00:00:00

pages

337-348

issue

2

eissn

0012-1797

issn

1939-327X

pii

db18-0903

journal_volume

68

pub_type

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