Although the impact of telomeres on physiology stands well established, a question remains: how do telomeres impact cellular functions at a molecular level? This is because current understanding limits the influence of telomeres to adjacent subtelomeric regions despite the wide-ranging impact of telomeres. Emerging work in two distinct aspects offers opportunities to bridge this gap. First, telomere-binding factors were found with non-telomeric functions. Second, locally induced DNA secondary structures called G-quadruplexes are notably abundant in telomeres, and gene regulatory regions genome wide. Many telomeric factors bind to G-quadruplexes for non-telomeric functions. Here we discuss a more general model of how telomeres impact the non-telomeric genome - through factors that associate at telomeres and genome wide - and influence cell-intrinsic functions, particularly aging, cancer, and pluripotency.

Institute of Biophysics of the CAS v v i Královopolská 135 612 65 Brno Czech Republic; Laboratoire d'Optique et Biosciences Ecole Polytechnique CNRS INSERM Institut Polytechnique de Paris 91128 Palaiseau France

Integrative and Functional Biology Unit CSIR Institute of Genomics and Integrative Biology New Delhi 110025 India; Academy of Scientific and Innovative Research Ghaziabad 201002 India

Integrative and Functional Biology Unit CSIR Institute of Genomics and Integrative Biology New Delhi 110025 India; Academy of Scientific and Innovative Research Ghaziabad 201002 India; GNR Knowledge Centre for Genome and Informatics CSIR Institute of Genomics and Integrative Biology New Delhi 110025 India

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