Transcriptional activators direct histone acetyltransferase complexes to nucleosomes.
Transcriptional co-activators were originally identified as proteins that act as intermediaries between upstream activators and the basal transcription machinery. The discovery that co-activators such as Tetrahymena and yeast Gcn5, as well as human p300/CBP, pCAF, Src-1, ACTR and TAFII250, can acetylate histones suggests that activators may be involved in targeting acetylation activity to promoters. Several histone deacetylases have been linked to transcriptional co-repressor proteins, suggesting that the action of both acetylases and deacetylases is important in the regulation of many genes. Here we demonstrate the binding of two native yeast histone acetyltransferase (HAT) complexes to the herpesvirus VP16 activation domain and the yeast transcriptional activator Gcn4, and show that it is their interaction with the VP16 activation domain that targets Gal4-VP16-bound nucleosomes for acetylation. We find that Gal4-VP16-driven transcription from chromatin templates is stimulated by both HAT complexes in an acetyl CoA-dependent reaction. Our results demonstrate the targeting of native HAT complexes by a transcription-activation domain to nucleosomes in order to activate transcription.
Utley
R T
RT
Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park 16802-4500, USA.
Ikeda
K
K
Grant
P A
PA
Côté
J
J
Steger
D J
DJ
Eberharter
A
A
John
S
S
Workman
J L
JL
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D001692:Biological Transport; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D017405:Herpes Simplex Virus Protein Vmw65 / Q000235:genetics / Q000378:metabolism*; D051548:Histone Acetyltransferases; D009097:Multienzyme Complexes / Q000378:metabolism; D016296:Mutagenesis; D009707:Nucleosomes / Q000378:metabolism*; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D005982:Glutathione Transferase; D017405:Herpes Simplex Virus Protein Vmw65; D051548:Histone Acetyltransferases; D009097:Multienzyme Complexes; D009707:Nucleosomes; D011494:Protein Kinases; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; C501392:GCN5 protein, S cerevisiae; D000099224:p300-CBP-Associated Factor