THE TRANSACTIVATION POTENTIAL OF VARIANT HEPATOCYTE NUCLEAR FACTOR-I IS MODIFIED BY ALTERNATIVE SPLICING

Two forms of the transcription factor vHNF1 (HNF1beta or LFB3) have be en previously described, derived by alternative splicing from a common premessenger RNA, and have been called vHNF1-A and vHNF1-B. vHNF1 pro teins share a homologous homeo-related DNA-binding domain with the HNF 1 protein, initially characterized as a liver-restricted transcription factor, and bind to a similar sequence motif. Here we demonstrate tha t vHNF1-A is a stronger transactivator than vHNF1-B when assayed in tr ansient transfections using two different promoters. vHNF1-A also bind s DNA with a higher affinity suggesting that a region of the protein l ocated immediately upstream of the homeodomain can modulate the protei n/DNA interaction and transactivation. Both vHNF1 transcripts were fou nd at a constant ratio in every tissue where vHNF1 expression could be detected, using a quantitative reverse transcriptase-polymerase chain reaction.