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PMID: 11914279 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Dynamics of global histone acetylation and deacetylation in vivo: rapid restoration of normal histone acetylation status upon removal of activators and repressors.

Genes & development ·Vol. 16 ·No. 6 ·2002-03-15 ·Pages 743-52

Katan-Khaykovich Y, Struhl K

Abstract

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.

MeSH Terms
Acetylation Alleles Chromatin/chemistry,metabolism DNA/metabolism Dose-Response Relationship, Drug Gene Expression Regulation Histone Deacetylases/metabolism Histones/metabolism Kinetics Nucleosomes/metabolism Polymerase Chain Reaction Precipitin Tests Promoter Regions, Genetic Time Factors Transcription, Genetic
Chemicals
Chromatin Histones Nucleosomes DNA Histone Deacetylases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Katan-Khaykovich Yael
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Struhl Kevin
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.967302
Published
2002-03-15
Pages
743-52
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC155357
Subset
IM
Grants
NIGMS NIH HHS · GM30186 · United States
NIGMS NIH HHS · GM53720 · United States
NIGMS NIH HHS · R01 GM030186 · United States
NIGMS NIH HHS · R37 GM030186 · United States
NIGMS NIH HHS · R01 GM053720 · United States
External Links
PubMed source DOI: 10.1101/gad.967302 PMC Full Text View journal details
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