Dissociation of the Hepatic Phenotype from HNF4 and HNF1x Expression

<div class="line" id="line-7"> Dedi&fflig;erentiated cells have served as tools to understand the molecular consequences of the loss of tissue-speci&filig;c pathways. Here we report the characterization of one of these cell lines, M29, which lacks the liver-enriched HNF4-HNF1x pathway, in order to determine if this class of variant cell lines could provide additional information regarding requirements for tissue-type expression. We report that although the liver-speci&filig;c x1-antitrypsin (a1AT) gene remains silent despite reactivation of the HNF4/HNF1x pathway in the M29 cells, the frequency of activation of an integrated x1AT-APRT transgene is increased 1000-fold in response to these transcription factors. The human x1AT locus (introduced via chromosome transfer) also remained silent on these cells, despite HNF4 and HNF1x expression. Results from cell fusion experiments suggest that the defect in the M29 cells is recessive. Results suggest that the M29 cells contain a defect that represses liver gene expression despite the presence of the HNF4/HNF1x pathway.</div>