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Originally published as MBC in Press, 10.1091/mbc.E08-05-0524 on September 17, 2008

Vol. 19, Issue 11, 4993-5005, November 2008

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HST3/HST4-dependent Deacetylation of Lysine 56 of Histone H3 in Silent Chromatin

Bo Yang, Andrew Miller, and Ann L. Kirchmaier

Department of Biochemistry and Purdue Cancer Center, Purdue University, West Lafayette, IN 47907

Submitted May 27, 2008; Revised August 19, 2008; Accepted September 5, 2008
Monitoring Editor: Kerry S. Bloom

The composition of posttranslational modifications on newly synthesized histones must be altered upon their incorporation into chromatin. These changes are necessary to maintain the same gene expression state at individual chromosomal loci before and after DNA replication. We have examined how one modification that occurs on newly synthesized histone H3, acetylation of K56, influences gene expression at epigenetically regulated loci in Saccharomyces cerevisiae. H3 K56 is acetylated by Rtt109p before its incorporation into chromatin during S phase, and this modification is then removed by the NAD+-dependent deacetylases Hst3p and Hst4p during G2/M phase. We found silenced loci maintain H3 K56 in a hypoacetylated state, and the absence of this modification in rtt109 mutants was compatible with HM and telomeric silencing. In contrast, loss of HST3 and HST4 resulted in hyperacetylation of H3 K56 within silent loci and telomeric silencing defects, despite the continued presence of Sir2p throughout these loci. These silencing defects in hst3{Delta} hst4{Delta} mutants could be suppressed by deletion of RTT109. In contrast, overexpression of Sir2p could not restore silencing in hst3{Delta} hst4{Delta} mutants. Together, our findings argue that HST3 HST4 play critical roles in maintaining the hypoacetylated state of K56 on histone H3 within silent chromatin.


This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E08-05-0524) on September 17, 2008.

Address correspondence to: Ann L. Kirchmaier (kirchmaier{at}purdue.edu).

Abbreviations used: ChIP, chromatin immunoprecipitation.




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