Transitions in Distinct Histone H3 Methylation Patterns at the Heterochromatin Domain Boundaries

TLDR

Eukaryotic genomes are organized into discrete structural and functional chromatin domains. Distinct H3 lysine‑9 and lysine‑4 methylation patterns, together with Swi6 binding, demarcate a 20‑kb silent heterochromatic interval and adjacent euchromatin in fission yeast, with inverted repeat boundaries preventing spreading of H3K9 methylation and the associated heterochromatin complexes from inhibiting H3K4 methylation.

Abstract

Eukaryotic genomes are organized into discrete structural and functional chromatin domains. Here, we show that distinct site-specific histone H3 methylation patterns define euchromatic and heterochromatic chromosomal domains within a 47-kilobase region of the mating-type locus in fission yeast. H3 methylated at lysine 9 (H3 Lys 9 ), and its interacting Swi6 protein, are strictly localized to a 20-kilobase silent heterochromatic interval. In contrast, H3 methylated at lysine 4 (H3 Lys 4 ) is specific to the surrounding euchromatic regions. Two inverted repeats flanking the silent interval serve as boundary elements to mark the borders between heterochromatin and euchromatin. Deletions of these boundary elements lead to spreading of H3 Lys 9 methylation and Swi6 into neighboring sequences. Furthermore, the H3 Lys 9 methylation and corresponding heterochromatin-associated complexes prevent H3 Lys 4 methylation in the silent domain.