Hepatocyte-specific promoter element HP1 of the Xenopus albumin gene interacts with transcriptional factors of mammalian hepatocytes

Abstract

By transfecting various Xenopus albumin-CAT fusion genes into the mouse hepatoma cell line BW1J a 13 base-pair hepatocyte-specific promoter element (HP1) could be identified. A similar sequence element is also present in the promoter of the albumin and alpha-fetoprotein genes of other vertebrates. Introduction of single point mutations into HP1 destroys its function. Binding studies with nuclear proteins identify a factor interacting with HP1 which is specific for hepatic cells. In-vitro transcription in a rat liver nuclear extract demonstrates that HP1 leads to an increased transcriptional activity. This increased transcription is specifically inhibited by the addition of an HP1-containing oligonucleotide, establishing that the interaction of factors with HP1 is essential for increased transcription. Since HP1 derived from a Xenopus gene functions in mammalian hepatocytes, we conclude that a regulatory system involved in liver-specific gene expression has been conserved during evolution.