Dynamics of global histone acetylation and deacetylation in vivo: rapid restoration of normal histone acetylation status upon removal of activators and repressors.
DNA-binding activators and repressors recruit histone acetylases and deacetylases to promoters, thereby generating localized domains of modified histones that influence transcriptional activity. At the end of a transcriptional response, alterations in histone acetylation status are reversed, but the dynamics of this process are poorly understood. Here, we recruit histone deacetylases and acetylases to a well-defined yeast promoter in a regulated manner. Following dissociation of the recruiting protein from the promoter, targeted deacetylation and acetylation are reversed with rapid, yet distinct, kinetics. Reversal of targeted deacetylation occurs within 5-8 min, whereas reversal of targeted acetylation is more rapid, taking 1.5 min. These findings imply that untargeted, globally acting enzymes generate a highly dynamic equilibrium of histone acetylation and deacetylation reactions across chromatin. Targeted acetylases and deacetylases can locally perturb this equilibrium, yet once they are removed, the global activities mediate a rapid return to the steady-state level of histone acetylation. Our results also indicate that TBP occupancy depends on the presence of the activator, not histone acetylation status.
Katan-Khaykovich
Yael
Y
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Struhl
Kevin
K
D000107:Acetylation; D000483:Alleles; D002843:Chromatin / Q000737:chemistry* / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D007700:Kinetics; D009707:Nucleosomes / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D013997:Time Factors; D014158:Transcription, Genetic
D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D004247:DNA; D006655:Histone Deacetylases