Cross-talk between histone H3 tails produces cooperative nucleosome acetylation.
Acetylation of histone proteins by the yeast Spt-Ada-Gcn5-acetyltansferase (SAGA) complex has served as a paradigm for understanding how posttranslational modifications of chromatin regulate eukaryotic gene expression. Nonetheless, it has been unclear to what extent the structural complexity of the chromatin substrate modulates SAGA activity. By using chromatin model systems, we have found that SAGA-mediated histone acetylation is highly cooperative (cooperativity constant of 1.97 +/- 0.15), employing the binding of multiple noncontiguous nucleosomes to facilitate maximal acetylation activity. Studies with various chromatin substrates, including those containing novel asymmetric histone octamers, indicate that this cooperativity occurs only when both H3 histone tails within a nucleosome are properly oriented and unacetylated. We propose that modulation of maximal SAGA activity through this dual-tail recognition could facilitate coregulation of spatially proximal genes by promoting cooperative nucleosome acetylation between genes.
Li
Shanshan
S
Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, Ames, IA 50011, USA.
Shogren-Knaak
Michael A
MA
D000107:Acetylation; D002843:Chromatin / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D007700:Kinetics; D009707:Nucleosomes / Q000378:metabolism*; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism
D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; C507785:SAGA complex, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators