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PMID: 12972612 Published · ppublish English Comparative Study Journal Article Research Support, U.S. Gov't, P.H.S.

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

Molecular and cellular biology ·Vol. 23 ·No. 19 ·2003-10-00 ·Pages 6944-57

Barlev NA, Emelyanov AV, Castagnino P, Zegerman P, Bannister AJ, Sepulveda MA, Robert F, Tora L, Kouzarides T, Birshtein BK, Berger SL

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, hAda2beta. Ada2beta differs both biochemically and functionally from the previously characterized hAda2alpha, which is a stable component of the human PCAF (human Gcn5 homologue) acetylase complex. Ada2beta, relative to Ada2alpha, interacted selectively, although not stably, with the Gcn5-containing histone acetylation complex TFTC/STAGA. In addition, Ada2beta 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, hAda2beta (but not Ada2alpha), 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 (Ada2beta) can coordinate targeting of both histone acetylation and chromatin remodeling activities.

MeSH Terms
Acetyltransferases/metabolism Adaptor Proteins, Signal Transducing Amino Acid Sequence Antigens, CD19/genetics,metabolism B-Lymphocytes/metabolism Base Sequence Carrier Proteins/chemistry,metabolism Cell Line DNA Helicases DNA-Binding Proteins/metabolism Glutathione Transferase/metabolism HeLa Cells Humans Molecular Sequence Data Nuclear Proteins/metabolism PAX5 Transcription Factor Promoter Regions, Genetic Protein Structure, Tertiary Recombinant Fusion Proteins/metabolism Sequence Homology, Amino Acid Trans-Activators/metabolism Transcription Factors/chemistry,metabolism Transcription, Genetic Transcriptional Activation
Chemicals
Adaptor Proteins, Signal Transducing Antigens, CD19 Carrier Proteins DNA-Binding Proteins Nuclear Proteins PAX5 Transcription Factor PAX5 protein, human Recombinant Fusion Proteins TADA2A protein, human TADA2B protein, human Trans-Activators Transcription Factors Acetyltransferases Glutathione Transferase SMARCA4 protein, human DNA Helicases
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Barlev Nickolai A
Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, Pennsylvania, USA.
Emelyanov Alexander V
Castagnino Paola
Zegerman Philip
Bannister Andrew J
Sepulveda Manuel A
Robert Flavie
Tora Laszlo
Kouzarides Tony
Birshtein Barbara K
Berger Shelley L
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.23.19.6944-6957.2003
Published
2003-10-00
Pages
6944-57
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC193946
Subset
IM
Grants
NIAID NIH HHS · AI 41572 · United States
NIAID NIH HHS · AI 13509 · United States
NIAID NIH HHS · R37 AI013509 · United States
NCI NIH HHS · CA78831 · United States
NIAID NIH HHS · R01 AI013509 · United States
NCI NIH HHS · R01 CA078831 · United States
External Links
PubMed source DOI: 10.1128/MCB.23.19.6944-6957.2003 PMC Full Text View journal details
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