It is now well known that chromatin structure and subnuclear environment play universal roles in the regulation of gene transcription and any type of DNA transactions, including the 3Rs (replication, recombination and repair). Most telomeres and subtelomeres from Saccharomyces cerevisiae to Homo sapiens repress neighboring genes by a mechanism named Telomere Position Effect (TPE). Such a widespread conservation among eukaryotes suggests a fundamental role of TPE for genome function.