Telomere Position Effect-Over Long Distances Acts as a Genome-Wide Epigenetic Regulator Through a Common Alu Element

Area of Science:

• Genomics
• Epigenetics
• Molecular Biology

Background:

• Telomeres, the protective caps of chromosomes, influence genome regulation through epigenetic modifications.
• Telomere Position Effect-Over Long Distances (TPE-OLD) describes how telomere length and proximity affect gene expression via long-range genomic interactions.

Purpose of the Study:

• To elucidate the molecular mechanisms underlying TPE-OLD.
• To identify cis-acting motifs and trans-acting factors involved in TPE-OLD.
• To investigate the role of telomere shortening in modulating gene expression through TPE-OLD.

Main Methods:

• Genome-wide transcriptome and methylome analysis in fibroblasts and myoblasts/myotubes with varying telomere lengths.
• Integration of omics data to identify TPE-OLD-associated genomic features and regulatory factors.
• Comparative analysis with human transcriptomic datasets, including the Genotype-Tissue Expression (GTEx) project.

Main Results:

• Identification of a common TPE-OLD-dependent cis-acting motif functioning as an insulator or enhancer.
• Discovery of trans partners regulating these motifs, with a notable depletion of RBPJ at TPE-OLD loci upon telomere shortening.
• Validation of findings through comparison with existing human transcriptomic data.

Conclusions:

• TPE-OLD operates at a genome-wide scale, mediated by RBPJ.
• RBPJ acts as a bridge, connecting Alu-like elements to telomeres to relay TPE-OLD.
• TPE-OLD, potentially involving Alu elements and RBPJ, may coordinate genome-wide telomere effects in response to physiological and pathological stimuli.