Methods and compositions are provided for modulating, e.g., increasing or decreasing, the expression of telomerase reverse transcriptase (TERT). In the subject methods, the binding interaction of the TERT Site C repressor site with a Site C repressor protein complex made up of one or more proteins is modulated to achieve the desired change in TERT expression. A feature of the subject invention is that the target Site C repressor protein complex includes an LSF protein. The subject methods and compositions find use in a variety of different applications, including the immortalization of cells, the production of reagents for use in life science research, therapeutic applications; therapeutic agent screening applications; and the like.