Histone acetyltransferase complexes can mediate transcriptional activation by the major glucocorticoid receptor activation domain.
Previous studies have shown that the Ada adapter proteins are important for glucocorticoid receptor (GR)-mediated gene activation in yeast. The N-terminal transactivation domain of GR, tau1, is dependent upon Ada2, Ada3, and Gcn5 for transactivation in vitro and in vivo. Using in vitro techniques, we demonstrate that the GR-tau1 interacts directly with the native Ada containing histone acetyltransferase (HAT) complex SAGA but not the related Ada complex. Mutations in tau1 that reduce tau1 transactivation activity in vivo lead to a reduced binding of tau1 to the SAGA complex and conversely, mutations increasing the transactivation activity of tau1 lead to an increased binding of tau1 to SAGA. In addition, the Ada-independent NuA4 HAT complex also interacts with tau1. GAL4-tau1-driven transcription from chromatin templates is stimulated by SAGA and NuA4 in an acetyl coenzyme A-dependent manner. Low-activity tau1 mutants reduce SAGA- and NuA4-stimulated transcription while high-activity tau1 mutants increase transcriptional activation, specifically from chromatin templates. Our results demonstrate that the targeting of native HAT complexes by the GR-tau1 activation domain mediates transcriptional stimulation from chromatin templates.
Wallberg
A E
AE
Karolinska Institute, Department of Biosciences, NOVUM, S-14157 Huddinge, Sweden. annika.wallberg@csb.ki.se
Neely
K E
KE
Gustafsson
J A
JA
Workman
J L
JL
Wright
A P
AP
Grant
P A
PA
D000123:Acetyltransferases / Q000378:metabolism*; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001665:Binding Sites / Q000235:genetics; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000378:metabolism; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009154:Mutation; D011494:Protein Kinases / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D051548:Histone Acetyltransferases; D046911:Macromolecular Substances; D011494:Protein Kinases; D011965:Receptors, Glucocorticoid; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C090575:ADA2 protein, S cerevisiae; C083323:NGG1 protein, S cerevisiae; C118425:SAGA protein, Emericella nidulans; C501392:GCN5 protein, S cerevisiae; D000099224:p300-CBP-Associated Factor