title: Hex stimulates the hepatocyte nuclear factor 1alpha-mediated activation of transcription.
abstract: The homeodomain protein Hex can function either as a transcriptional repressor or activator in animals. Recent reports have indicated that Hex is involved in liver development. However, its target genes and interacting proteins are largely unknown. We found that Hex functionally interacted with hepatocyte nuclear factor (HNF) 1alpha to further stimulate its activity using reporter gene containing multiple copies of HNF1alpha-binding site of the L-type pyruvate kinase (L-PK) gene promoter or natural L-PK promoter. This stimulation required the homeodomain and the acidic carboxyl-terminal region of Hex. Over-expression of Hex in primary cultured hepatocytes resulted in stimulation of the L-PK gene expression. Glutathione S-transferase pull-down assay and co-immunoprecipitation revealed that Hex physically interacted with HNF1alpha in mammalian cells through the homeodomain of Hex and POU-homeodomain of HNF1alpha. Since HNF1alpha is an important liver-enriched transcription factor involved in liver differentiation, Hex may contribute to liver differentiation through interaction with HNF1alpha.
authors.affiliation: Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa-ku, Nagoya 464-8601, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Tanaka
authors.forename: Taichi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ban
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Satoh
authors.forename: Takashi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Masafumi
authors.initials: M
authors.lastname: Shimoda
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Miyazaki
authors.forename: Tamio
authors.initials: T
authors.lastname: Noguchi
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D005786:Gene Expression Regulation / Q000502:physiology*; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011770:Pyruvate Kinase / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology
chemical_list: D018398:Homeodomain Proteins; D014157:Transcription Factors; D005982:Glutathione Transferase; D011770:Pyruvate Kinase