A novel human Ada2 homologue functions with Gcn5 or Brg1 to coactivate transcription

Nickolai A. Barlev, Alexander V. Emelyanov, Paola Castagnino, Philip Zegerman, Andrew J. Bannister, Manuel A. Sepulveda, Flavie Robert, Laszlo Tora, Tony Kouzarides, Barbara K. Birshtein, Shelley L. Berger

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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.

Original languageEnglish (US)
Pages (from-to)6944-6957
Number of pages14
JournalMolecular and cellular biology
Volume23
Issue number19
DOIs
StatePublished - Oct 1 2003

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Barlev, N. A., Emelyanov, A. V., Castagnino, P., Zegerman, P., Bannister, A. J., Sepulveda, M. A., Robert, F., Tora, L., Kouzarides, T., Birshtein, B. K., & Berger, S. L. (2003). A novel human Ada2 homologue functions with Gcn5 or Brg1 to coactivate transcription. Molecular and cellular biology, 23(19), 6944-6957. https://doi.org/10.1128/MCB.23.19.6944-6957.2003