Subtelomere-specific condensed chromatin is regulated by three different histone modifications

In fission yeast, telomere-adjacent subtelomeres form a subtelomere-specific condensed chromatin structure, referred to as a knob, requiring histone H2A-S121 phosphorylation-dependent localization of Sgo2 at subtelomeres during interphase. However, the mechanism underlying specific Sgo2 localization in subtelomeres remains unclear. Our genetic screen identified Nts1, a histone deacetylase complex component, as a regulator of Sgo2 localization. Nts1 localized to subtelomeres during interphase and influenced histone H4 acetylation. The deletion of both Nts1 and Set2, a histone H3-K36 methyltransferase, led to the loss of Sgo2 at subtelomeres. These findings indicate that H4 deacetylation and H3-K36 methylation redundantly determine Sgo2 localization under H2A-S121 phosphorylation.