Generation of inhibitory mutants of hepatocyte nuclear factor 4.
Hepatocyte nuclear factor 4 (HNF-4) is a member of the nuclear-receptor gene superfamily. HNF-4 binds to response elements of several liver-enriched genes and exhibits a restricted pattern of expression, suggesting an important role for HNF-4 in tissue-specific gene regulation. Here, we report the generation of three mutated forms of the HNF-4 protein, their effects on the ability of the protein to transactivate through HNF-4-response elements, and their ability to suppress transactivation by the wild-type protein. Two mutated forms of the HNF-4 protein, one in which the DNA-binding domain has been deleted and another in which the HNF-4 proximal box has been replaced by that of the glucocorticoid receptor, behaved as inhibitors of the wild-type protein. The properties of a carboxy-terminal-deletion mutant allow us to propose a region of HNF-4 involved in transactivation.
Taraviras
S
S
German Cancer Research Center, Division Molecular Biology of the Cell I, Heidelberg.
Schütz
G
G
Kelsey
G
G
D000595:Amino Acid Sequence; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D001665:Binding Sites / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics; D006367:HeLa Cells; D051557:Hepatocyte Nuclear Factor 4; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010750:Phosphoproteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics; D017384:Sequence Deletion; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics*; D015533:Transcriptional Activation; D014162:Transfection
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D017931:DNA Primers; D004268:DNA-Binding Proteins; D051557:Hepatocyte Nuclear Factor 4; C403128:MLX protein, human; D010750:Phosphoproteins; D018160:Receptors, Cytoplasmic and Nuclear; D011965:Receptors, Glucocorticoid; D011994:Recombinant Proteins; D014157:Transcription Factors