Epigenetics of Human Telomeres.

Abstract

Human telomeric heterochromatin is unusual in that it does not show the enrichment of canonical repressive histone marks H3K9me3 or H4K20me3 seen in constitutive heterochromatin. Instead, human telomeres exhibit both facultative heterochromatin and euchromatin marks, consistent with their epigenetically regulated transcription into TERRA noncoding RNA. Additionally, telomeric DNA is out of phase with the DNA helical repeat and has no nucleosome positioning signal. Yet, human telomeric DNA forms a columnar structure of tightly stacked nucleosomes, alternating with open states, and regulated by histone tails and shelterin protein binding. We discuss the proposed mechanisms regulating human telomeric chromatin and the consequences that telomeric chromatin properties have on various cellular processes, such as telomere transcription, the regulation of shelterin binding, and the activation of the alternative lengthening of telomeres mechanism. Together, we summarize current evidence on the combination of hetero- and euchromatic properties of human telomeres that may help explain their crucial protective functions and plasticity to regulate telomere maintenance pathways and damage signaling.