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Dissociation of the Hepatic Phenotype from HNF4 and HNF1α Expression

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Bioscience Reports

Dedifferentiated cells have served as tools to understand the molecular consequences of the loss of tissue-specific pathways. Here we report the characterization of one of these cell lines, M29, which lacks the liver-enriched HNF4-HNF1α 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-specific α1-antitrypsin (α1AT) gene remains silent despite reactivation of the HNF4/HNF1α pathway in the M29 cells, the frequency of activation of an integrated α1AT-APRT transgene is increased 1000-fold in response to these transcription factors. The human α1AT locus (introduced via chromosome transfer) also remained silent on these cells, despite HNF4 and HNF1α 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/HNF1α pathway.

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  1. Department of Biological Sciences, Eastern Illinois University, 600 Lincoln Avenue, Charleston, IL, 61920, USA

    Gary A. Bulla & David M. Kraus

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Correspondence to Gary A. Bulla.

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Bulla, G.A., Kraus, D.M. Dissociation of the Hepatic Phenotype from HNF4 and HNF1α Expression. Biosci Rep 24, 595–608 (2004). https://doi.org/10.1007/s10540-005-2794-8

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