Cloning and DNA‐binding properties of the rat pancreatic β‐cell‐specific factor Nkx6.1
- 15 November 1999
- journal article
- Published by Wiley in FEBS Letters
- Vol. 461 (3) , 287-294
- https://doi.org/10.1016/s0014-5793(99)01436-2
Abstract
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.Keywords
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