Foxa2, a novel protein partner of tumour suppressor menin, is deregulated in mouse and human MEN1 glucagonomas

Rémy Bonnavion, Romain Teinturier, Samuele Gherardi, Emmanuelle Leteurtre, Run Yu, Martine Cordier-Bussat, Rui Du, François Pattou, Marie-Christine Vantyghem, Philippe Bertolino, Jieli Lu, Chang Xian Zhang

Foxa2, known as one of the pioneer factors, plays a crucial role in islet development and endocrine functions. Its expression and biological functions are regulated by various factors, including in particular insulin and glucagon. However, its expression and biological role in the adult pancreatic α-cells remain elusive. In the current study, we showed that Foxa2 was overexpressed in islets from α-cell-specific Men1 mutant mice, both at the transcriptional and protein levels. More importantly, immunostaining analyses detected its prominent nuclear accumulation, specifically in α-cells, at a very early stage after Men1-disruption. A similar nuclear FOXA2 expression was also detected in a substantial proportion (12/19) of human MEN1 glucagonomas. Interestingly, our data revealed an interaction between Foxa2 and menin encoded by the Men1 gene. Furthermore, using several approaches, we demonstrated the relevance of this interaction in the regulation of two tested Foxa2 target genes, including the auto-regulation of the Foxa2 promoter by Foxa2 itself. The current study establishes menin, a novel protein partner of Foxa2, as a regulator of Foxa2, the biological functions of which are beyond the pancreatic endocrine cells.

Share this article

February, 2017


Related product

  • Bioruptor-pico-next-gen-sequencing
    Bioruptor® Pico sonication device


  • "Molecular Biosystems" Conference on Eukaryotic Gene Regulation and Functional Genomics
    Puerto Varas, Región de Los Lagos, Chile
    Sep 23-Sep 26, 2017
  • The 76th Annual Meeting of the Japanese Cancer Association
    Tokyo, Japan
    Sep 28-Sep 30, 2017
 See all events

Twitter feed


 See all news