title: Rescue of the HNF4 --> HNF1alpha pathway in hepatoma variant cells containing human chromosome 12.
abstract: Expression of liver-enriched trans-acting hepatocyte nuclear factors 1alpha (HNF1alpha) and 4 (HNF4) is correlated with the hepatic phenotype in cultured rat hepatoma cells. We have used a hepatoma variant cell line, H11, that specifically lacks the HNF4 --> HNF1alpha pathway as a model to understand mechanisms controlling hepatic gene expression. We have introduced randomly marked human chromosomes into H11 cells and have isolated a number of microcell hybrids that have rescued hepatic gene expression, including HNF4, HNF1alpha, and alpha1-antitrypsin. Chromosomal analysis of cell hybrids showed that the rescued hepatic phenotype correlated closely with the presence of human chromosome 12p sequences. Although the gene encoding HNF1alpha is located on chromosome 12q24, its retention was not required to rescue the hepatic phenotype. Thus, we suggest that a locus on human chromosome 12p plays an important role in maintenance of hepatic gene expression through activation of the HNF4 --> HNF1alpha pathway.
authors.affiliation: Department of Pediatrics, Pediatric Research Institute, St. Louis University Health Sciences Center and Cardinal Glennon Children's Hospital, St. Louis, Missouri, 63110, USA. bullaga@slu.edu
authors.forename: G A
authors.initials: GA
authors.lastname: Bulla
authors.forename: J R
authors.initials: JR
authors.lastname: Batanian
authors.forename: H M
authors.initials: HM
authors.lastname: Young
authors.forename: N
authors.initials: N
authors.lastname: Bradley
authors.forename: N
authors.initials: N
authors.lastname: Kazi
authors.forename: B R
authors.initials: BR
authors.lastname: Haddad
mesh_terms: D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D002478:Cells, Cultured; D002881:Chromosomes, Human, Pair 12; D002896:Chromosomes, Human, Pair 6; D002897:Chromosomes, Human, Pair 7; D004268:DNA-Binding Proteins; D015870:Gene Expression; D005816:Genetic Complementation Test; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D051557:Hepatocyte Nuclear Factor 4; D006801:Humans; D006822:Hybrid Cells; D009687:Nuclear Proteins; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes; D000515:alpha 1-Antitrypsin / Q000235:genetics / Q000378:metabolism
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D051557:Hepatocyte Nuclear Factor 4; C496489:Hnf1a protein, rat; C403128:MLX protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; D014157:Transcription Factors; D000515:alpha 1-Antitrypsin; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta