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Heritable chromatin structure: mapping "memory" in histones H3 and H4
Christine M Smith1, Zara W Haimberger, Catherine O Johnson
1Division of Basic Sciences and Proteomics Facility, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA.
Summary
Histone H4 lysine 12 acetylation acts as a memory mark for heritable gene silencing at telomeres in yeast. This epigenetic mark ensures the propagation of either active or silenced gene states.
Area of Science:
- Epigenetics
- Molecular Biology
- Yeast Genetics
Background:
- The telomeric position effect in Saccharomyces cerevisiae involves heritable gene silencing.
- Gene silencing is propagated, suggesting an epigenetic memory mechanism.
- Posttranslational modification of chromatin was proposed to mediate this heritability.
Purpose of the Study:
- To identify chromatin sites acting as "memory" for heritable gene transmission.
- To isolate mutant histone H3 and H4 alleles that lock telomeric genes in a silenced state.
Main Methods:
- Genetic screen for histone H3 and H4 mutants affecting telomeric silencing.
- Mass spectrometry (MS) to quantify histone H4 tail acetylation levels.
Main Results:
- Mutations were identified in histone H3 and H4 NH(2)-terminal tails and cores.
- Mutations mapped near known acetylation/methylation sites.
- A significant reduction in histone H4 lysine 12 acetylation was observed in mutants.
Conclusions:
- Histone H4 lysine 12 (K12) acetylation functions as an epigenetic "memory mark".
- Unacetylated K12 propagates silent chromatin inheritance.
- Acetylated K12 propagates active gene expression inheritance.