Histone Modifications and the Maintenance of Telomere Integrity

Abstract

Telomeres, the nucleoprotein structures at the ends of eukaryotic chromosomes, play an integral role in protecting linear DNA from degradation. Dysregulation of telomeres can result in genomic instability and has been implicated in increased rates of cellular senescence and many diseases, including cancer. The integrity of telomeres is maintained by a coordinated network of proteins and RNAs, such as the telomerase holoenzyme and protective proteins that prevent the recognition of the telomere ends as a DNA double-strand breaks. The structure of chromatin at telomeres and within adjacent subtelomeres has been implicated in telomere maintenance pathways in model systems and humans. Specific post-translational modifications of histones, including methylation, acetylation, and ubiquitination, have been shown to be necessary for maintaining a chromatin environment that promotes telomere integrity. Here we review the current knowledge regarding the role of histone modifications in maintaining telomeric and subtelomeric chromatin, discuss the implications of histone modification marks as they relate to human disease, and highlight key areas for future research.

Telomeres and Telomere Length: A General Overview

“…Besides the routine post-translational modifications, histone proteins function in telomere capping, telomere transcription, homologous recombination at telomeres, cellular differentiation, and nuclear reprogramming [29,34]. The heterochromatin structure transcriptionally silences nearby genes, a phenomenon attributed to the telomere position effect (TPE) [34]. TPE mainly involves the shelterin protein, repressor and activator protein 1 (RAP1), and histone acetylase, SIRT6, a homolog of the yeast protein silent information regulator 2 (Sir2).…”

DNA Methyltransferases in Cancer: Biology, Paradox, Aberrations, and Targeted Therapy

“…Histone methylation mainly occurs on lysine and arginine residues of histones H3 and H4, histone methyltransferase can selectively methylate lysines and arginines in the tails of histones, and synergistically induce transcriptional activity. Moreover, when histone acetylation in chromatin is in a loose state, which is conducive to gene expression [ 9 , 10 ]. In addition to the coding part of nucleic acid plays an important role in gene expression, and functional non-coding RNA also plays an important role in gene expression.…”

Epigenetic Histone Modifications in the Pathogenesis of Diabetic Kidney Disease

“… 48 The post-translational modification (PTM) of histones is the main mechanism to regulate chromatin structure, commonly occurring on the amino acid residues lysine, arginine, serine, tyrosine, and threonine and ultimately influencing transcriptional activity. 49 The enzymes that mediate histone modification including acetyltransferases, methyltransferases are called epigenetic writers; deacetylases and demethylases are called epigenetic erasers; and proteins recognizing acetylated proteins at promoters and enhancers are called epigenetic readers (for example, bromodomain-containing protein 4). 50–52 …”