Genomic characterization reveals a simple histone H4 acetylation code
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Edited by Mark T. Groudine, Fred Hutchinson Cancer Research Center, Seattle, WA, and approved February 28, 2005 (received for review January 6, 2005)
Abstract
The histone code hypothesis holds that covalent posttranslational modifications of histone tails are interpreted by the cell to yield a rich combinatorial transcriptional output. This hypothesis has been the subject of active debate in the literature. Here, we investigated the combinatorial complexity of the acetylation code at the four lysine residues of the histone H4 tail in budding yeast. We constructed yeast strains carrying all 15 possible combinations of mutations among lysines 5, 8, 12, and 16 to arginine in the histone H4 tail, mimicking positively charged, unacetylated lysine states, and characterized the resulting genome-wide changes in gene expression by using DNA microarrays. Only the lysine 16 mutation had specific transcriptional consequences independent of the mutational state of the other lysines (affecting ≈100 genes). In contrast, for lysines 5, 8, and 12, expression changes were due to nonspecific, cumulative effects seen as increased transcription correlating with an increase in the total number of mutations (affecting ≈1,200 genes). Thus, acetylation of histone H4 is interpreted by two mechanisms: a specific mechanism for lysine 16 and a nonspecific, cumulative mechanism for lysines 5, 8, and 12.
Footnotes
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↵ * To whom correspondence should be addressed. E-mail: orando{at}cgr.harvard.edu.
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Author contributions: O.J.R. designed research; M.F.D. performed research; S.J.A., L.F.W., and O.J.R. analyzed data; and O.J.R. wrote the paper.
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This paper was submitted directly (Track II) to the PNAS office.
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See Commentary on page 5308.
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Freely available online through the PNAS open access option.
- Copyright © 2005, The National Academy of Sciences
