Int J Biol Sci 2013; 9(9):934-946. doi:10.7150/ijbs.7529 This issue Cite

Research Paper

SIRT1 Deacetylates FOXA2 and Is Critical for Pdx1 Transcription and β-Cell Formation

Rui-Hong Wang1, Xiaoling Xu1, Hyun-Seok Kim1, Zhen Xiao2, Chu-Xia Deng1 ✉

1. Genetics of Development and Disease Branch, 10/9N105, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland MD 20892, USA;
2. Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland 21702, USA.

Citation:
Wang RH, Xu X, Kim HS, Xiao Z, Deng CX. SIRT1 Deacetylates FOXA2 and Is Critical for Pdx1 Transcription and β-Cell Formation. Int J Biol Sci 2013; 9(9):934-946. doi:10.7150/ijbs.7529. https://www.ijbs.com/v09p0934.htm
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Abstract

Pancreas duodenum homeobox 1 (PDX1) is essential for pancreas development and β-cell formation; however more studies are needed to clearly illustrate the precise mechanism regarding spatiotemporal regulation of Pdx1 expression during β-cell formation and development. Here, we demonstrate that SIRT1, FOXA2 and a number of proteins form a protein complex on the promoter of the Pdx1 gene. SIRT1 and PDX1 are expressed in the same set of cells during β-cell differentiation and maturation. Pancreas-specific disruption of SIRT1 diminished PDX1 expression and impaired islet development. Consequently, SIRT1 mutant mice develop progressive hyperglycemia, glucose intolerance, and insulin insufficiency, which directly correlate with the extent of SIRT1 deletion. We further show that SIRT1 interacts with and deacetylates FOXA2 on the promoter of the Pdx1gene, and positively regulates its transcription. These results uncover an essential role of SIRT1 in β-cell formation by maintaining expression of PDX1 and its downstream genes, and identify pancreas-specific SIRT1 mutant mice as a relevant model for studying insulin insufficiency.

Keywords: SIRT1, FOXA2, PDX1, insulin.


Citation styles

APA
Wang, R.H., Xu, X., Kim, H.S., Xiao, Z., Deng, C.X. (2013). SIRT1 Deacetylates FOXA2 and Is Critical for Pdx1 Transcription and β-Cell Formation. International Journal of Biological Sciences, 9(9), 934-946. https://doi.org/10.7150/ijbs.7529.

ACS
Wang, R.H.; Xu, X.; Kim, H.S.; Xiao, Z.; Deng, C.X. SIRT1 Deacetylates FOXA2 and Is Critical for Pdx1 Transcription and β-Cell Formation. Int. J. Biol. Sci. 2013, 9 (9), 934-946. DOI: 10.7150/ijbs.7529.

NLM
Wang RH, Xu X, Kim HS, Xiao Z, Deng CX. SIRT1 Deacetylates FOXA2 and Is Critical for Pdx1 Transcription and β-Cell Formation. Int J Biol Sci 2013; 9(9):934-946. doi:10.7150/ijbs.7529. https://www.ijbs.com/v09p0934.htm

CSE
Wang RH, Xu X, Kim HS, Xiao Z, Deng CX. 2013. SIRT1 Deacetylates FOXA2 and Is Critical for Pdx1 Transcription and β-Cell Formation. Int J Biol Sci. 9(9):934-946.

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