Role of Histone H3 Lysine 9 Methylation in Epigenetic Control of Heterochromatin Assembly

TLDR

Higher‑order chromatin assembly is linked to covalent modifications of histone tails. In fission yeast, Clr4‑mediated methylation of H3 Lys9 at heterochromatic regions, requiring its chromo‑ and SET domains, is essential for Swi6 localization and, together with Clr3 and Rik1, establishes a conserved histone‑code pathway that epigenetically inherits heterochromatin assembly.

Abstract

The assembly of higher order chromatin structures has been linked to the covalent modifications of histone tails. We provide in vivo evidence that lysine 9 of histone H3 (H3 Lys 9 ) is preferentially methylated by the Clr4 protein at heterochromatin-associated regions in fission yeast. Both the conserved chromo- and SET domains of Clr4 are required for H3 Lys 9 methylation in vivo. Localization of Swi6, a homolog of Drosophila HP1, to heterochomatic regions is dependent on H3 Lys 9 methylation. Moreover, an H3-specific deacetylase Clr3 and a β-propeller domain protein Rik1 are required for H3 Lys 9 methylation by Clr4 and Swi6 localization. These data define a conserved pathway wherein sequential histone modifications establish a “histone code” essential for the epigenetic inheritance of heterochromatin assembly.