Spreading of Sir3 protein in cells with severe histone H3 hypoacetylation
- Arnold Kristjuhan*,†,
- Birgitte Ø. Wittschieben*,†,‡,
- Jane Walker*,
- Douglas Roberts§,
- Bradley R. Cairns§, and
- Jesper Q. Svejstrup*,¶
- *Mechanisms of Transcription Laboratory, Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, United Kingdom; and §Howard Hughes Medical Institute and Department of Oncological Science, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112
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Communicated by Roger D. Kornberg, Stanford University School of Medicine, Stanford, CA, April 17, 2003 (received for review November 18, 2002)
Abstract
Heterochromatin formation in yeast involves deacetylation of histones, but the precise relationship between acetylation and the association of proteins such as Sir3, Sir4, and the histone deacetylase Sir2 with chromatin is still unclear. Here we show that Sir3 protein spreads to subtelomeric DNA in cells lacking the transcription-related histone acetyltransferases GCN5 and ELP3. Spreading correlates with hypoacetylation of lysines in the histone H3 tail and results in deacetylation of lysine 16 in histone H4. De-repression of genes situated very close to the ends of the chromosomes in gcn5 elp3 suggests that Sir3 spreads into subtelomeric DNA from the tip of the telomere. Interestingly, growth defects caused by gcn5 elp3 mutation can be suppressed by SIR deletion, suggesting that Sir proteins become detrimental for growth when chromatin is severely hypoacetylated.
Footnotes
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↵ ¶ To whom correspondence should be addressed. E-mail: j.svejstrup{at}cancer.org.uk.
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↵ † A.K. and B.Ø.W. contributed equally to this work.
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↵ ‡ Present address: University of Pittsburgh Cancer Institute, Hillman Cancer Center Research Pavilion, 5117 Centre Avenue, Suite 264, Pittsburgh, PA 15213.
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Abbreviation: ChIP, chromatin immunoprecipitation.
- Copyright © 2003, The National Academy of Sciences
