ROLES OF HISTONE H3T6 PHOSPHORYLATION IN HETEROCHROMATIN MAINTENANCE IN FISSION YEAST

Abstract

Threonine 6 is a highly conserved residue in the N-terminal tail of histone H3. In vitro studies suggest the inhibitory effect of phosphorylated H3T6 to various lysine specific binding proteins. However, the roles of this phosphorylation mark in cellular processes that underlie genomic stability remain unclear. In this project, a non-phosphorylatable mutant H3T6A was constructed in the model organism Schizosaccharomyces pombe. Genome-wide transcriptomic analysis revealed massive up-regulation of transcription in heterochromatized domains at the centromeres and sub-telomeres in H3T6A mutant. H3T6A mutant showed mislocalization of heterochromatin proteins Swi6, Chp1, and reduction of methylated H3K9, indicative of the disruption of heterochromatic integrity. Consistently, H3T6A mutant cells exhibited high percentage of chromosome missegregation and hypersensitivity towards the microtubule destabilizing drug thiabendazole. Phosphorylation of H3T6 residue was detected on the centromeric heterochromatin preferentially during the early S-phase. In conclusion, phosphorylation of H3T6 is important for genomic stability via maintaining integrity in heterochromatic areas.