The histone code hypothesis posits that distinct combinations of histone modifications can recruit chromatin-modifying enzymes and exert epigenetic control over heterochromatin assembly. In the March 15 ScienceXpress, Nakayama et al. describe a role for histone methylation in heterochromatin assembly in the fission yeast Schizosaccharomyces pombe. The Clr4 protein methylated lysine 9 of histone H3 (H3Lys9) preferentially within heterochromatin-associated regions. H3Lys9 methylation led to the recruitment of the chromodomain protein Swi6, a homolog of Drosophila HP1. Both methylation and recruitment were dependent on activity of the histone deacetylase Clr3. Chromatin assembly by Swi6/Clr4 at the mating-type locus results in silencing. Hence, sequential deacetylation and methylation of histone tails leads ultimately to epigenetic inheritance patterns.

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