Walker Lab

Wayne State University Medical School

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


Journal article


H. Cyphert, E. Walker, Y. Hang, S. Dhawan, Rachana Haliyur, Lauren Bonatakis, D. Avrahami, M. Brissova, K. Kaestner, A. Bhushan, A. Powers, R. Stein
Diabetes, 2018

Semantic Scholar DOI PubMedCentral PubMed
Cite

Cite

APA   Click to copy
Cyphert, H., Walker, E., Hang, Y., Dhawan, S., Haliyur, R., Bonatakis, L., … Stein, R. (2018). Examining How the MAFB Transcription Factor Affects Islet β-Cell Function Postnatally. Diabetes.


Chicago/Turabian   Click to copy
Cyphert, H., E. Walker, Y. Hang, S. Dhawan, Rachana Haliyur, Lauren Bonatakis, D. Avrahami, et al. “Examining How the MAFB Transcription Factor Affects Islet β-Cell Function Postnatally.” Diabetes (2018).


MLA   Click to copy
Cyphert, H., et al. “Examining How the MAFB Transcription Factor Affects Islet β-Cell Function Postnatally.” Diabetes, 2018.


BibTeX   Click to copy

@article{h2018a,
  title = {Examining How the MAFB Transcription Factor Affects Islet β-Cell Function Postnatally},
  year = {2018},
  journal = {Diabetes},
  author = {Cyphert, H. and Walker, E. and Hang, Y. and Dhawan, S. and Haliyur, Rachana and Bonatakis, Lauren and Avrahami, D. and Brissova, M. and Kaestner, K. and Bhushan, A. and Powers, A. and Stein, R.}
}

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.