NUCLEAR RECEPTOR COACTIVATOR ACTR IS A NOVEL HISTONE ACETYLTRANSFERASE AND FORMS A MULTIMERIC ACTIVATION COMPLEX WITH P CAF AND CBP/P300/

We report here the identification of a novel cofactor, ACTR, that dire ctly binds nuclear receptors and stimulates their transcriptional acti vities in a hormone-dependent fashion. ACTR also recruits two other nu clear factors, CBP and P/CAF, and thus plays a central role in creatin g a multisubunit coactivator complex. In addition, and unexpectedly, w e show that purified ACTR is a potent histone acetyltransferase and ap pears to define a distinct evolutionary branch to this recently descri bed family. Thus, hormonal activation by nuclear receptors involves th e mutual recruitment of at least three classes of histone acetyltransf erases that may act cooperatively as an enzymatic unit to reverse the effects of histone cleacetylase shown to be part of the nuclear recept or corepressor complex.