The glucocorticoid receptor functions at multiple steps during transcription initiation by RNA polymerase II

Lain J. McEwan, Tova Almlöf, Ann Charlotte Wikström, Karin Dahlman-Wright, Anthony P.H. Wright, Jan Åke Gustafsson

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

We have used a panel of monoclonal antibodies and a cell-free transcription assay to study the function of the τ1 transactivation domain of the human glucocorticoid receptor. Three antibodies (monoclonal antibodies 250, 275, and 286) specifically inhibited τ1-dependent transcription, but had little or no effect on either basal transcription or the activity of an unrelated yeast transcription factor. This inhibition was not due to interference of DNA binding activity, as all three antibodies super shifted τ1-containing protein-DNA complexes. Epitopes for all three antibodies were localized to a region between amino acids 190 and 200, which lies within the recently defined 41-amino acid core region of τ1 that is required for transactivation (Dahlman-Wright, K., Almlof, T., McEwan, I.J., Gustafsson, J.-A., and Wright, A.P.H. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 1619- 1623). In contrast to the effect on τ1-dependent transcription none of the antibodies tested antagonized the squelching ability of the τ1 domain, suggesting that τ1-mediated transactivation involves interactions in addition to those identified by the squelching assay. Consistent with this, a comparison of the kinetics of τ1 squelching and inhibition of transactivation by monoclonal antibodies suggested a role for τ1 mediated transcriptional induction at two or more steps during transcription initiation by RNA polymerase II.

Original languageEnglish (US)
Pages (from-to)25629-25636
Number of pages8
JournalJournal of Biological Chemistry
Volume269
Issue number41
StatePublished - Oct 14 1994

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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