14-3-3ζ interacts with hepatocyte nuclear factor 1α and enhances its DNA binding and transcriptional activation

•14-3-3ζ interacted with HNF1α.•14-3-3ζ affected HNF1α transactivity and target gene levels.•14-3-3ζ is recruited on endogenous HNF1α cis elements and enhances its DNA-binding.•HNF1αSer247 phosphorylation contributes to the 14-3-3ζ binding.

14-3-3 proteins regulate numerous cellular processes through interaction with a variety of proteins, and have been identified as HNF1α binding partner by mass spectrometry analysis in our previous study. In the present study, the interaction between 14-3-3ζ and HNF1α has been further validated by in vivo and in vitro assays. Moreover, we have found that overexpression of 14-3-3ζ potentiated the transcriptional activity of HNF1α in cultured cells, and silencing of 14-3-3ζ by RNA interference in HepG2 cells specifically affected the HNF1α-dependent gene expression. Furthermore, we have demonstrated that 14-3-3ζ is recruited to endogenous HNF1α responsive promoters and enhances HNF1α binding to its cognate DNA sequences. In addition, we have also provided evidence that the association between HNF1α and 14-3-3ζ is phosphorylation-dependent. Taken together, these results suggest that 14-3-3ζ may be an endogenous physiologic regulator of HNF1α.