Functional association between CBP and HNF4 in trans-activation.

CBP functions as a key transcriptional coactivator for a variety of transcription factors. We show here that the hepatocyte nuclear factor 4 (HNF4), a transcription factor in the nuclear receptor superfamily with no defined ligand, is cloned by yeast two-hybrid system using CBP as a bait. GST-pull down assay with nuclear extracts or in vitro translation products revealed that CBP and HNF4 interact with each other at the middle portion (aa 119-375) of HNF4 and two distinct regions (aa 271-451 and 1626-2259) of CBP, respectively, in the ligand-independent manner. Co-transfection experiments indicated that CBP is capable of activating HNF4 site-mediated transcription. These results suggested a functional association between CBP and HNF4 in trans-activation.