Columnar structure of human telomeric chromatin

Abstract

Telomeres, the ends of eukaryotic chromosomes, play pivotal roles in ageing and cancer and are targets of DNA damage and response. However, little is known about the structure and organization of telomeric chromatin at the molecular level. We used electron microscopy and single-molecule magnetic tweezers to characterize well-defined telomeric chromatin fibers of kilobasepair length. The cryo-EM structure of the compact telomeric tetranucleosome revealed a novel columnar folding, unusually short nucleosome repeat length of ~132bp and the role of the histone N-terminal tails in stabilizing this structure. This is the first near-high resolution structure of chromatin with a native DNA sequence. The columnar structure exposes the DNA, making them susceptible to DNA damage. The telomeric tetranucleosome also exists in an alternative well-defined state, with one nucleosome open, accessible to protein factors. This suggests that protein factors, which plays a role in maintaining telomeres, can bind to telomeric chromatin in its compact heterochromatic form. The features of the telomeric chromatin structure reveals important insights of significant relevance for telomere function in vivo that provides information on mechanisms of nucleosome recognition by chromatin factors

Histone H1 protects telomeric repeats from H3K27me3 invasion inArabidopsis

“…For instance, H1 has been proposed to be underrepresented at telomeres in plants 92,94 as it is in mammals 88,[95][96][97] . This could explain the short NRL of Arabidopsis and human telomeres 92,98 that, long after being suspected 99 , have recently been re-constructed as a H1-free state columnar organization 100 . In conclusion, the existence of distinct chromatin states at Arabidopsis telomeres needs to be explored in more detail to establish whether the H1-mediated repression of PRC2 activity is a global property of telomeres or rather impacts a few segments.…”

Multiscale Bayesian Simulations Reveal Functional Chromatin Condensation of Gene Loci

“…S5). Notably, the landscape includes significant populations of tetranucleosomes resembling experimentally determined structures stabilized by either i,i+1 (9) (Fig. 5A, bottom right) or i,i+2 (10, 11) (Fig.…”

“…From the 1CPN metainference simulations, we first explored the local organization of the Nanog locus chromatin fibers. We focused our analysis on tetranucleosomes as the fundamental units of the fiber organization (9–11, 13). We performed principal component analysis (PCA) (43) of all tetranucleosome contact maps within the 10kb Nanog locus in all the 128 metainference replicas.…”

“…For example, nucleosomal DNA sliding and unwrapping from histones modulate transcription factor (TF) binding (6)(7)(8), with downstream effects on gene expression. At a higher hierarchical level, these nucleosomes interact together to form chromatin fibers exhibiting remarkable structural polymorphism (9)(10)(11). In vivo, these fibers are predominantly disordered (12), but specific chromatin motifs are associated with distinct genomic regions, such as gene promoters or gene bodies (13).…”

Nucleosomes at the Dawn of Eukaryotes

“…The position of individual histones within the complex is fixed, as is its overall size. (There are, of course, exceptions: assembly intermediates naturally contain fewer than eight histones and there are variant complexes such as hemisomes, which assemble on centromeric DNA ( Dalal et al 2007 ), hexasomes ( Baer and Rhodes 1983 ), and telomeric nucleosomes, where octamers are present but stacked in direct contact with each other to form larger contiguous histone–DNA complexes ( Soman et al 2022 ). These exceptions, however, are typically rare in number and exist alongside the classic, hetero-octameric nucleosomes, which make up the bulk of eukaryotic chromatin.)…”