Telomere-proximal DNA in Saccharomyces cerevisiae is refractory to methyltransferase activity in vivo.

Genes located near telomeres in Saccharomyces cerevisiae undergo position-effect variegation; their transcription is subject to reversible but mitotically heritable repression. This position effect and the finding that telomeric DNA is late replicating suggest that yeast telomeres exist in a heterochromatin-like state. Mutations in genes that suppress the telomeric position effect suggest that a special chromatin structure exists near chromosomal termini. Thus transcriptional repression may be explained by the inability of DNA binding proteins to access the DNA near telomeres. To test this hypothesis, the Escherichia coli Dam DNA methyltransferase, which modifies the sequence GATC, was introduced into S. cerevisiae cells. DNA sequences near the telomere were highly refractive to Dam methylation but were modified when located at positions more internal on the chromosome. Telomeric sequences were accessible to methyltransferase activity in strains that contained a mutation that suppressed the telomeric position effect. These data support the model that sequence-specific DNA binding proteins are excluded from telomere-proximal sequences in vivo and show that expression of DNA methyltransferase activity may serve as a useful tool for mapping chromosomal structural domains in vivo.