A complex network of interactions governs DNA methylation at telomeric regions

Abstract

DNA methylation modulates telomere function. In Arabidopsis thaliana, telomeric regions have a bimodal chromatin organization with unmethylated telomeres and methylated subtelomeres. To gain insight into this organization we have generated TAIR10-Tel, a modified version of the Arabidopsis reference genome with additional sequences at most chromosome ends. TAIR10-Tel has allowed us to analyse DNA methylation at nucleotide resolution level in telomeric regions. We have analysed the wild-type strain and mutants that encode inactive versions of all currently known relevant methyltransferases involved in cytosine methylation. These analyses have revealed that subtelomeric DNA methylation extends 1 to 2 kbp from Interstitial Telomeric Sequences (ITSs) that abut or are very near to telomeres. However, DNA methylation drops at the telomeric side of the telomere-subtelomere boundaries and disappears at the inner part of telomeres. We present a comprehensive and integrative model for subtelomeric DNA methylation that should help to decipher the mechanisms that govern the epigenetic regulation of telomeres. This model involves a complex network of interactions between methyltransferases and subtelomeric DNA sequences.

Histone H1 protects telomeric repeats from H3K27me3 invasion inArabidopsis

“…A limitation of our study is that we could not assess the precise distribution of HK27me3 enrichment along each telomere. In agreement with the mosaic chromatin status of telomeres in other organisms 91 , Arabidopsis telomeres are thought to be made of segments with distinct nucleosome repeat length (NRL). With average length of 150 bp 92 , this is much shorter than the 189 bp estimated for H1-rich TEs 23 .…”

Epigenetic nature of Arabidopsis thaliana telomeres

“…The absence of heterochromatic marks enrichment at Arabidopsis telomeres might seem surprising considering its repetitiveness and that pericentromeric and subtelomeric ITSs are heterochromatic ( Vaquero-Sedas et al, 2011 ; Farrell et al, 2022 ). However, the unique characteristics of telomeric sequences and their nucleosomal organization should contribute to explain why telomeres are not labeled with heterochromatic marks (see below).…”

“…Since subtelomeric heterochromatin is enriched in H3K9me2, antibodies recognizing H3K9me2 might immunoprecipitate subtelomeric DNA fragments containing the centromeric side of telomeres with low frequency. Even more, these antibodies could directly immunoprecipitate the centromeric side of telomeres within the telomere–subtelomere boundaries, which undergo very low levels of cytosine methylation ( Farrell et al, 2022 ). This border effect would not be observed for H3K27me1 because the levels of this epigenetic mark within subtelomeric heterochromatin are lower than those of H3K9me2 (M.I.…”

Atlas of telomeric repeat diversity inArabidopsis thaliana

“…This telomere-adjacent region serves as a transition zone between the telomere and the rest of the chromosome that contains genes and other genetic elements (Churikov and Price 2008). Specific types of variant telomeric repeats have been implicated in determining methylation state (Farrell et al 2022), protein binding (Wang et al 2023) and formation of G-quadruplexes (Lee and Kim 2009). A comprehensive understanding of the evolutionary dynamics and functional significance of telomeres and telomere-adjacent regions must therefore begin with thorough knowledge of variation in the composition of telomeric repeats.…”

“…Subsequently, sequencing of PCR products revealed the heterogeneity of variant repeats from individual chromosome ends (Wang et al 2010; Kuo 2006). Variant repeats have also been directly observed in unassembled sequencing reads (Choi et al 2021), and they have been identified by partially assembling four chromosome ends in the Col-0 accession from Illumina short reads (Farrell et al 2022). However, the highly repetitive nature of telomeric regions, the presence of identical sequences shared between repeat-adjacent regions, as well as large interstitial telomeric arrays in other parts of A. thaliana genomes create ambiguity when mapping reads that are only hundreds base pairs long to specific positions of the genome (Olson et al 2023; Teano et al 2023; Heacock et al 2004).…”