Molecular basis of TPE-OLD [methylation]

Among epigenetic modifiers, telomeres, represent attractive modulators of the genome in part through position effects. Telomere Position Effect – Over Long Distances (TPE-OLD) modulates genes expression by changes in telomeric-dependent long-distance loops, with a reach of 10Mb from the telomeres. However, TPE-OLD remain poorly defined. We used cells with controlled telomere length combined to a genome wide approach revealing its transcriptome and methylome. We identified a common cis element that behaved as an insulator/ enhancer. By using reporter assays integrating this element, we disclosed additional trans partners further validated by in silico data. Exploiting our cellular model we observed the depletion of one candidate (RBPJ) at TPE-OLD associated loci concomitant to telomere shortening. Therefore, we conclude that TPE-OLD is orchestrated by Alu-like elements acting as enhancers in association with RBPJ. We propose that TPE-OLD functions by the coordinated action of newly evolved enhancers; an associated protein RBPJ and telomere length to produce an adapted response to external stimuli (i.e., Aging) DNA methylation analysis Of Myoblasts, Myotubes and Fibroblasts with short and long telomeres