Telomerase Reverse Transcriptase (TERT) in Action: Cross-Talking with Epigenetics

• Published in: International journal of molecular sciences 2019-07, Vol.20 (13), p.3338
• Main Authors: Yuan, Xiaotian, Xu, Dawei
• Format: Article
• Language: English
• Subjects: aging; Animals; Binding; cancer; Cell growth; Cell proliferation; Chromatin Assembly and Disassembly - genetics; Chromatin remodeling; CpG islands; Crosstalk; Deoxyribonucleic acid; DNA; DNA methylation; DNA Methylation - genetics; Epigenesis, Genetic; Epigenetics; Gene expression; Gene silencing; Histone deacetylase; Humans; Laboratory animals; Medicin och hälsovetenskap; Models, Genetic; Mutation; Older people; Phenotypes; Review; RNA-directed DNA polymerase; Senescence; Somatic cells; Telomerase; Telomerase - metabolism; Telomerase reverse transcriptase; telomerase reverse transcriptase (TERT); Telomere - metabolism; telomere lengthening; Tumor suppressor genes; Tumorigenesis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20133338

Telomerase, an RNA-dependent DNA polymerase with telomerase reverse transcriptase (TERT) as the catalytic component, is silent due to the tight repression of the gene in most normal human somatic cells, whereas activated only in small subsets of cells, including stem cells, activated lymphocytes, and other highly proliferative cells. In contrast, telomerase activation via TERT induction is widespread in human malignant cells, which is a prerequisite for malignant transformation. It is well established that TERT/telomerase extends telomere length, thereby conferring sustained proliferation capacity to both normal and cancerous cells. The recent evidence has also accumulated that TERT/telomerase may participate in the physiological process and oncogenesis independently of its telomere-lengthening function. For instance, TERT is shown to interact with chromatin remodeling factors and to regulate DNA methylation, through which multiple cellular functions are attained. In the present review article, we summarize the non-canonical functions of TERT with a special emphasis on its cross-talk with epigenetics: How TERT contributes to epigenetic alterations in physiological processes and cancer, and how the aberrant epigenetics in turn facilitate TERT expression and function, eventually promoting cancer either initiation or progression or both. Finally, we briefly discuss clinical implications of the TERT-related methylation.