Open AccessDelineation of a small region within the majortransactivation domain of the human glucocorticoid receptor that mediatestransactivation of gene expression.
Author(s) -
Karin Dahlman-Wright,
Tova Almlöf,
Iain J. McEwan,
Jan Åke Gustafsson,
Andrew N. Wright
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.5.1619
Subject(s) - transactivation , glucocorticoid receptor , nuclear receptor coactivator 2 , biology , c terminus , transcription factor , microbiology and biotechnology , gene , amino acid , nuclear receptor , biochemistry
Previous deletion analysis localized the majortransactivation function of the human glucocorticoid receptor to a 185-aminoacid segment close to the N terminus of the receptor protein. This region wasnamed tau 1 [Hollenberg, S. M. & Evans, R. M. (1988) Cell 55, 899-906]. Todelineate the smallest active region within tau 1, we have systematically testedthe transactivation capacity of deletion derivatives of the tau 1 domain, fusedto the glucocorticoid receptor DNA-binding domain, in yeast cells. Internalscanning deletions suggested that residues near the C terminus of tau 1 are mostimportant for activity. Deletions of N-terminal and C-terminal sequencesidentified a 41-amino acid "core" region near the C terminus of tau 1that is crucial for tau 1 function. Small peptide fragments containing the tau 1core region are competent for transactivation, while regions outside the tau 1core are not active. We have previously demonstrated that the intact tau 1domain squelches the activity of a minimal promoter in vivo and in vitro,suggesting involvement of interactions with a component/components of the basaltranscription machinery in the mechanism of transactivation. This activity wasmaintained in the tau 1 core-containing segments.