Assessing the Epigenetic Status of Human Telomeres

Abstract

The epigenetic modifications of human telomeres play a relevant role in telomere functions and cell proliferation. Therefore, their study is becoming an issue of major interest. These epigenetic modifications are usually analyzed by microscopy or by chromatin immunoprecipitation (ChIP). However, these analyses could be challenged by subtelomeres and/or interstitial telomeric sequences (ITSs). Whereas telomeres and subtelomeres cannot be differentiated by microscopy techniques, telomeres and ITSs might not be differentiated in ChIP analyses. In addition, ChIP analyses of telomeres should be properly controlled. Hence, studies focusing on the epigenetic features of human telomeres have to be carefully designed and interpreted. Here, we present a comprehensive discussion on how subtelomeres and ITSs might influence studies of human telomere epigenetics. We specially focus on the influence of ITSs and some experimental aspects of the ChIP technique on ChIP analyses. In addition, we propose a specific pipeline to accurately perform these studies. This pipeline is very simple and can be applied to a wide variety of cells, including cancer cells. Since the epigenetic status of telomeres could influence cancer cells proliferation, this pipeline might help design precise epigenetic treatments for specific cancer types.

Epigenetic nature of Arabidopsis thaliana telomeres

“…Alternatively, enhanced levels of euchromatic marks might be detected at telomeres due a border effect. This border effect entails the influence of subtelomeric chromatin on ChIP-hyb or ChIP-seq analyses of telomeres, as previously discussed ( Vaquero-Sedas and Vega-Palas, 2019 ). Its magnitude should depend on the length of telomeres and of the immunoprecipitated chromatin fragments.…”

“…In addition, ChIP analyses of telomeres should be properly controlled. Hence, studies focused on the epigenetic features of telomeres have to be carefully designed and interpreted ( Vaquero-Sedas and Vega-Palas, 2019 ).…”

Mega‐sized pericentromeric blocks of simple telomeric repeats and their variants reveal patterns of chromosome evolution in ancient Cycadales genomes

“…Telomeric repeats are known to exhibit numerous unique chromatin features, including short nucleosome repeat lengths and distinct epigenetic modifications (Fojtova & Fajkus, 2020 ; Vaquero‐Sedas & Vega‐Palas, 2019 ). At the cytogenetic level, our data show that the pericentromeric blocks of telomeric repeats clearly overlap with the 5‐mC signals in C. revoluta (Figure S4a ).…”

Epigenetic Characteristics of Human Subtelomeres Vary in Cells Utilizing the Alternative Lengthening of Telomeres (ALT) Pathway

“…Telomere packaging as heterochromatin was considered essential for suppressing ALT [ 22 , 54 ]; however, recent studies support the enrichment of H3K9me3 at ALT telomeres, indicating that a shift to heterochromatic characteristics is a hallmark of the ALT pathway [ 48 , 49 ]. Subtelomeric chromatin is not necessarily identical to telomeric chromatin, and a specific histone modification in ALT+ cells may play a different role at subtelomeres compared to telomeric repeats (reviewed in [ 55 , 56 ]). In this study, we considered the potential role for TERRA in ALT activation and, therefore, concentrated on determining whether distal subtelomeric regions encompassing TERRA promoters exhibit distinct H3K4me3 and H3K9me3 patterns in ALT+ cells compared to WT fibroblasts.…”