Expanding heterochromatin reveals discrete subtelomeric domains delimited by chromatin landscape transitions

Abstract

The eukaryotic genome is divided into chromosomal domains of heterochromatin and euchromatin. Transcriptionally silent heterochromatin is found at subtelomeric regions, leading to the telomeric position effect (TPE) in yeast, fly and man. Heterochromatin generally initiates and spreads from defined loci, and diverse mechanisms prevent the ectopic spread of heterochromatin into euchromatin. Here, we overexpressed the silencing factor Sir3 at various levels in yeast, and found that Sir3 spreading into Extended Silent Domains (ESD) eventually reached saturation at subtelomeres. We observed that Sir3 spreading into ESDs covered zone associated with specific histone marks in wild-type cells and stopped at zones of histone mark transitions including H3K79 tri-methylation levels. The conserved enzyme Dot1 deposits H3K79 methylation, and we found that it is essential for viability upon overexpression of Sir3, but not of a spreading-defective mutant Sir3A2Q. These data suggest that H3K79 methylation actively blocks Sir3 spreading. Lastly, our metaanalysis uncovers previously uncharacterized discrete subtelomeric domains associated with specific chromatin features offering a new viewpoint on how to separate subtelomeres from the core chromosome.

A proteomic screen of Ty1 integrase partners identifies the protein kinase CK2 as a regulator of Ty1 retrotransposition

“…Ty1 de novo integrations were assigned to the corresponding genomic feature. Analyses were performed using inhouse R pipelines (http://www.R-project.org), to compare the associations of integration profiles (both in vivo and in silico) with selected genomic features (subtelomeres (88), telomeres, retrotransposons, ARS and random, 1 x 10 5 Ty1 random insertions generated in silico).…”