DNA Methylation as a Candidate Mechanism Behind Stress-Attributed Telomere Shortening

Abstract

A network of proteins and enzymes facilitate the regulation of telomeres, but research is still unclear regarding the mechanism that underlies telomere maintenance. In brief, telomerase, an enzyme made up of subunits hTERT and hRT, adds telomeric repeats on the ends of chromosomes. Previous literature have observed significant telomere shortening on the ends of chromosomes in disadvantaged individuals exposed chronic stressors when compared to their advantaged counterparts. Alongside these studies, preliminary results have suggested that genes involved in maintaining telomere length may be regulated by DNA methylation, an epigenetic mechanism. In particular, the gene Mad1L1, a negative regulator of hTERT, was found to be positively correlated with telomere length. Our study aims to unpack plausible mechanisms that are connected to telomere maintenance. In doing so, our objective is to perform a functional assay to understand stress-associated DNA methylation and its effects on telomere biology. To develop a basis for this functional assay, we attempted to construct a necessary positive control, comprising of the prMTM1 promoter region and pCpGL vector backbone. Future directions include the construction of the experimental vector with prMad1L1 region and a Dual-Luciferase Promoter Functional Assay with this experimental construct.