ARRA: Telomerase in Inflammation and Atherosclerosis

Telomerase is essential for multiple developmental processes and exhibits two activities that profoundly influence cell activation, differentiation, inflammation and proliferation. By maintaining the stability of telomeres, DNA-protein complexes that protect the ends of chromosomes, telomerase is rate limiting for tissue renewal. Since most somatic cells repress the telomerase reverse transcriptase (TERT) catalytic core, telomeres shorten progressively during tissue renewal ultimately limiting lifespan and leading to cellular senescence. In addition to telomere maintenance, mounting evidence suggests that TERT modulates essential signaling pathways and serves a direct regulatory role in the activation of gene expression. Recent microarray analyses have consistently identified changes in global gene expression profiles upon overexpression of TERT without apparent involvement of its well-established function in telomere homeostasis. Although the mechanisms underlying this second, non-canonical activity of TERT remain elusive, the activation of chromosomally clustered genes and the generation of a chromatin architecture allowing active gene transcription by TERT in these recent studies point to novel properties of TERT in the epigenetic control of gene expression.