A heterochromatin domain forms gradually at a new telomere and is highly dynamic at stable telomeres

Abstract

Heterochromatin domains play important roles in chromosome biology, organismal development and aging. In the fission yeast Schizosaccharomyces pombe and metazoans, heterochromatin is marked by histone H3 lysine 9 dimethylation. While factors required for heterochromatin have been identified, the dynamics of heterochromatin formation are poorly understood. Telomeres convert adjacent chromatin into heterochromatin. To form a new heterochromatic region in S. pombe, an inducible DNA double-strand break (DSB) was engineered next to 48 bp of telomere repeats in euchromatin, which caused formation of new telomere and gradual spreading of heterochromatin. However, spreading was highly dynamic even after the telomere had reached its stable length. The system also revealed the presence of repeats located at the boundaries of euchromatin and heterochromatin that are oriented to allow the efficient healing of a euchromatic DSB to cap the chromosome end with a new telomere. Telomere formation in S. pombe therefore reveals novel aspects of heterochromatin dynamics and the presence of failsafe mechanisms to repair subtelomeric breaks, with implications for similar processes in metazoan genomes.