A Novel Human Ada2 Homologue Functions with Gcn5 or Brg1 To Coactivate Transcription

Abstract

In yeast, the transcriptional adaptor yeast Ada2 (yAda2) is a part of the multicomponent SAGA complex, which possesses histone acetyltransferase activity through action of the yGcn5 catalytic enzyme. yAda2, among several SAGA proteins, serves to recruit SAGA to genes via interactions with promoter-bound transcription factors. Here we report identification of a new human Ada2 homologue, hAda2β. Ada2β differs both biochemically and functionally from the previously characterized hAda2α, which is a stable component of the human PCAF (human Gcn5 homologue) acetylase complex. Ada2β, relative to Ada2α, interacted selectively, although not stably, with the Gcn5-containing histone acetylation complex TFTC/STAGA. In addition, Ada2β interacted with Baf57 (a component of the human Swi/Snf complex) in a yeast two-hybrid screen and associated with human Swi/Snf in vitro. In functional assays, hAda2β (but not Ada2α), working in concert with Gcn5 (but not PCAF) or Brg1 (the catalytic component of hSwi/Snf complex), increased transcription via the B-cell-specific transcription factor Pax5/BSAP. These findings support the view that Gcn5 and PCAF have distinct roles in vivo and suggest a new mechanism of coactivator function, in which a single adaptor protein (Ada2β) can coordinate targeting of both histone acetylation and chromatin remodeling activities.

ACKNOWLEDGMENTS

We thank Paul Moore for initial help in identifying the hAda2β gene and Gavin Schnitzler for the gift of purified hSwi/Snf. We also thank G. Moore, D. Sterner, and members of the Berger lab for helpful discussions and critical reading of the manuscript.

The research was supported by National Institute of Health grants to S.L.B. (CA78831) and to B.K.B. (AI 13509 and AI 41572).

N.A.B. and A.V.E. contributed equally to this study.