Cloning and DNA‐binding properties of the rat pancreatic β‐cell‐specific factor Nkx6.1

FEBS Letters

Serup, Palle¹  Vestergård Petersen, Helle¹  Madsen, Ole Dragsbæk¹  Jørgensen, Mette Christine¹  Ericson, Johan² 

[1] Department of Developmental Biology, Hagedorn Research Institute, Niels Steensensvej 6, DK-2820 Gentofte, Denmark;Department of Cell and Molecular Biology, Karolinska Institute, Doktorsringen 2D, S-17177 Stockholm, Sweden

关键词: Nkx6.1;    Pancreatic β-cell;    Cloning;    DNA-binding site;   

DOI  :  10.1016/S0014-5793(99)01436-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The homeodomain (HD) protein Nkx6.1 is the most β-cell-specific transcription factor known in the pancreas and its function is critical for the formation of the insulin-producing β-cells. However, the target genes, DNA-binding site, and transcriptional properties of Nkx6.1 are unknown. Using in vitro binding site selection we have identified the DNA sequence of the Nkx6.1 binding site to be TTAATTG/A. A reporter plasmid containing four copies of this sequence is activated by an Nkx6.1HD/VP16 fusion construct. Full-length Nkx6.1 fails to activate this reporter plasmid in spite of robust interaction with the binding site in vitro. Stable expression of Nkx6.1 in the glucagon-producing α-cell-like MSL-G-AN cells induces expression of the endogenous insulin gene in a subset of the cell population. The expression of other known β-cell-specific factors such as Pax4, Pax6, Pdx1, GLUT2 and GLP1-R is unchanged by the introduction of Nkx6.1.

【 授权许可】

Unknown