Open AccessGeneration of Inhibitory Mutants of Hepatocyte Nuclear Factor 4
Author(s) -
Taraviras Stavros,
SchüTz Günther,
Kelsey Gavin
Publication year - 1997
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1997.00883.x
Subject(s) - transactivation , hepatocyte nuclear factor 4 , hepatocyte nuclear factors , mutant , nuclear receptor , biology , transcription factor , gene , microbiology and biotechnology , nuclear localization sequence , dna binding domain , nuclear protein , glucocorticoid receptor , genetics
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 trans activate through HNF‐4–response elements, and their ability to suppress trans activation 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the HNF‐4 protein, one in which the DNA‐binding domain has been deleted and another in which the HNF‐4 proximal box has been replaced by that of the glucocorticoid receptor, behaved as inhibitors of the wild‐type protein.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 trans activation.