The transactivation potential of variant hepatocyte nuclear factor 1 is modified by alternative splicing.

Two forms of the transcription factor vHNF1 (HNF1 beta or LFB3) have been previously described, derived by alternative splicing from a common premessenger RNA, and have been called vHNF1-A and vHNF1-B. vHNF1 proteins share a homologous homeo-related DNA-binding domain with the HNF1 protein, initially characterized as a liver-restricted transcription factor, and bind to a similar sequence motif. Here we demonstrate that vHNF1-A is a stronger transactivator than vHNF1-B when assayed in transient transfections using two different promoters. vHNF1-A also binds DNA with a higher affinity suggesting that a region of the protein located immediately upstream of the homeodomain can modulate the protein/DNA interaction and transactivation. Both vHNF1 transcripts were found at a constant ratio in every tissue where vHNF1 expression could be detected, using a quantitative reverse transcriptase-polymerase chain reaction.