Novel features of telomere biology revealed by the absence of telomeric DNA methylation

Vega-Vaquero, Alejandro; Bonora, Giancarlo; Morselli, Marco; Vaquero-Sedas, María I.; Rubbi, Liudmilla; Pellegrini, Matteo; Vega-Palas, Miguel A.

doi:10.1101/gr.202465.115

Cited by 19 publications

(30 citation statements)

References 65 publications

(105 reference statements)

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“…In summary, we have seen that telomeres in most of the commonly studied human cell lines are not heterochromatic but exhibit euchromatic marks. However, heterochromatin is known to play a major role in telomere biology, which suggests that the integrity of subtelomeric heterochromatin might be important for the proper functioning of telomeres, as previously proposed for A. thaliana ( 10 , 14 ). Interestingly, we have also seen that certain cancer cells that maintain their telomeres through ALT have heterochromatic levels of H3K9me3 in their telomeres.…”

Section: Discussionmentioning

confidence: 61%

Epigenetic features of human telomeres

Cubiles

Barroso

Vaquero-Sedas

et al. 2018

Nucleic Acids Research

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Although subtelomeric regions in humans are heterochromatic, the epigenetic nature of human telomeres remains controversial. This controversy might have been influenced by the confounding effect of subtelomeric regions and interstitial telomeric sequences (ITSs) on telomeric chromatin structure analyses. In addition, different human cell lines might carry diverse epigenetic marks at telomeres. We have developed a reliable procedure to study the chromatin structure of human telomeres independently of subtelomeres and ITSs. This procedure is based on the statistical analysis of multiple ChIP-seq experiments. We have found that human telomeres are not enriched in the heterochromatic H3K9me3 mark in most of the common laboratory cell lines, including embryonic stem cells. Instead, they are labeled with H4K20me1 and H3K27ac, which might be established by p300. These results together with previously published data argue that subtelomeric heterochromatin might control human telomere functions. Interestingly, U2OS cells that exhibit alternative lengthening of telomeres have heterochromatic levels of H3K9me3 in their telomeres.

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Section: Discussionmentioning

confidence: 61%

Epigenetic features of human telomeres

Cubiles

Barroso

Vaquero-Sedas

et al. 2018

Nucleic Acids Research

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“…There has been considerable debate concerning the presence of DNA methylation at A. thaliana telomeres and its impact on telomere length (Cokus et al 2008; Vrbsky et al 2010; Vega-Vaquero et al 2016). One group reported that plants lacking RDR2, a core component of the DNA methylation pathway at asymmetric cytosines (such as telomeric repeats), do not display any telomere length dysregulation (Vrbsky et al 2010), while other studies, including this one, find telomere shortening in plants lacking DDM1 (Ogrocka et al 2014; Vaquero-Sedas and Vega-Palas 2014).…”

Section: Discussionmentioning

confidence: 99%

“…One group reported that plants lacking RDR2, a core component of the DNA methylation pathway at asymmetric cytosines (such as telomeric repeats), do not display any telomere length dysregulation (Vrbsky et al 2010), while other studies, including this one, find telomere shortening in plants lacking DDM1 (Ogrocka et al 2014; Vaquero-Sedas and Vega-Palas 2014). Recent data indicate that subtelomeric sequences flanking telomere repeats, not telomeric DNA itself, are subject to methylation (Vega-Vaquero et al 2016). Thus, it has been proposed that changes in telomeric chromatin are responsible for telomere shortening in ddm1 mutants (Vaquero-Sedas et al 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Two groups reported that A. thaliana telomeres are methylated by asymmetrical DNA methylation pathways directed by RNA-dependent DNA methylation (RdDM) (Cokus et al 2008; Vrbsky et al 2010). More recent studies suggest that the extent of DNA methylation at telomeres may be quite low or confined to subtelomeric regions (Vaquero-Sedas et al 2011; Ogrocka et al 2014; Vega-Vaquero et al 2016). While both telomeric and subtelomeric regions of yeast and mammal chromosomes are exclusively heterochromatic (Blasco 2007; Ottaviani et al 2008), subtelomeric regions in A. thaliana are reported to contain euchromatic (H3K4 Me2 and H3K9 Ac ) as well as heterochromatic (H3K9 Me2 and H3K27 Me ) features (Vaquero-Sedas et al 2011, 2012; Vrbsky et al 2010).…”

Section: Introductionmentioning

confidence: 99%

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DDM1 guards against telomere truncation in Arabidopsis

Xie

Shippen

2018

Plant Cell Rep

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Epigenetic pathways, including DNA methylation, are crucial for telomere maintenance. Deficient in DNA Methylation 1 (DDM1) encodes a nucleosome remodeling protein, required to maintain DNA methylation in Arabidopsis thaliana. Plants lacking DDM1 can be self-propagated, but in the sixth generation (G6) hypomethylation leads to rampant transposon activation and infertility. Here we examine the role of DDM1 in telomere length homeostasis through a longitudinal study of successive generations of ddm1-2 mutants. We report that bulk telomere length remains within the wild-type range for the first five generations (G1–G5), and then precipitously drops in G6. While telomerase activity becomes more variable in later generation ddm1-2 mutants, there is no correlation between enzyme activity and telomere length. Plants lacking DDM1 also exhibit no dysregulation of several known telomere-associated transcripts, including TERRA. Instead, telomere shortening coincides with increased G-overhangs and extra-chromosomal circles, consistent with deletional recombination. Telomere shortening also correlates with transcriptional activation of retrotransposons, and a hypersensitive DNA damage response in root apical meristems. Since abiotic stresses, including DNA damage, stimulate homologous recombination, we hypothesize that telomere deletion in G6 ddm1-2 mutants is a by-product of elevated genome-wide recombination in response to trans-poson mobilization. Further, we speculate that telomere truncation may be beneficial in adverse environmental conditions by accelerating the elimination of stem cells with aberrant genomes.

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“…Methylation studies of telomeric sequences, as with studies of the post-translational modifications of histones, have yielded ambiguous results. In Arabidopsis thaliana, one study showed the presence of methylation in telomeric sequences [47], whereas another study indicated the lack of methylation in this region [48]. In turn, DNA methylation of the telomeric and subtelomeric regions in three cotton species (G. hirsutum, G. herbaceum and G. arboreum) showed interspecific variation [49].…”

Section: Plos Onementioning

confidence: 99%

The distribution pattern of 5-methylcytosine in rye (Secale L.) chromosomes

Kalinka

Achrem

2020

PLoS ONE

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The rye (Secale L.) genome is large, and it contains many classes of repetitive sequences. Secale species differ in terms of genome size, heterochromatin content, and global methylation level; however, the organization of individual types of sequences in chromosomes is relatively similar. The content of the abundant subtelomeric heterochromatin fraction in rye do not correlate with the global level of cytosine methylation, hence immunofluorescence detection of 5-methylcytosine (5-mC) distribution in metaphase chromosomes was performed. The distribution patterns of 5-methylcytosine in the chromosomes of Secale species/subspecies were generally similar. 5-methylcytosine signals were dispersed along the entire length of the chromosome arms of all chromosomes, indicating high levels of methylation, especially at retrotransposon sequences. 5-mC signals were absent in the centromeric and telomeric regions, as well as in subtelomeric blocks of constitutive heterochromatin, in each of the taxa studied. Pericentromeric domains were methylated, however, there was a certain level of polymorphism in these areas, as was the case with the nucleolus organizer region. Sequence methylation within the region of the heterochromatin intercalary bands were also demonstrated to be heterogenous. Unexpectedly, there was a lack of methylation in rye subtelomeres, indicating that heterochromatin is a very diverse fraction of chromatin, and its epigenetic regulation or potential influence on adjacent regions can be more complex than has conventionally been thought. Like telomeres and centromeres, subtelomeric heterochromatin can has a specific role, and the absence of 5-mC is required to maintain the heterochromatin state.

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Novel features of telomere biology revealed by the absence of telomeric DNA methylation

Cited by 19 publications

References 65 publications

Epigenetic features of human telomeres

Epigenetic features of human telomeres

DDM1 guards against telomere truncation in Arabidopsis

The distribution pattern of 5-methylcytosine in rye (Secale L.) chromosomes

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