RNA polymerase II elongator holoenzyme is composed of two discrete subcomplexes

Elongator is a histone acetyltransferase complex that associates with the e longating form of RNA polymerase IL We purified Elongator to virtual homoge neity via a rapid three-step procedure based largely on affinity chromatogr aphy. The purified factor, holo-Elongator, is a labile six-subunit factor c omposed of two discrete subcomplexes: one comprised of the previously ident ified Elp1, Elp2, and Elp3 proteins and another comprised of three novel po lypeptides, termed Elp4, Elp5, and Elp6. Disruption of the yeast genes enco ding the new Elongator proteins confers phenotypes indistinguishable from t hose previously described for the other elp mutants, and concomitant disrup tion of genes encoding proteins in either subcomplex does not confer new ph enotypes. Taken together, our results indicate that holo-Elongator is a fun ctional entity in vitro as well as in vivo. Metazoan homologues of Elp1 and Elp3 have previously been reported. We cloned the human homologue of yeast ELP4 and show that this gene is ubiquitously expressed in human tissues.