Topological Diversity of Chromatin Fibers: Interplay Between Nucleosome Repeat Length, DNA Linking Number and the Level of Transcription

Norouzi, Davood; Katebi, Ataur; Nikitina, Tatiana; Zhurkin, Victor B.

doi:10.1016/j.bpj.2015.11.2201

Cited by 9 publications

(25 citation statements)

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“…We obtained this result rigorously [18,34], evaluating the Wr and DLk values through calculations of the Gauss double integral [41,42]. At the qualitative level, it is illustrated in Fig.…”

Section: Topological Polymorphism Of Chromatin Fibersmentioning

confidence: 92%

“…First, because in all these fiber structures, the DNA trajectories are similar, with DLk estimated to vary between -1.4 to -1.3 [34], which differs significantly from DLk = -1.0 measured for SV40 minichromosome [28,29] and later, for the plasmids containing 5S DNA repeats [35]. Second, in the published X-ray and cryo-EM structures of oligonucleosomal arrays [7,8] the linkers contain integral number of DNA turns (L=20, 30, 40 bp, denoted here as {10n}), whereas biochemical [36,37] and genomic studies [38][39][40] show prevalence of the linkers with half-integral numbers of DNA turns (denoted as {10n+5}).…”

Section: Topological Polymorphism Of Chromatin Fibersmentioning

confidence: 98%

“…To address this issue, we systematically analyzed stereochemically feasible two-start fibers, with the linker lengths varying in a wide interval from 10 to 70 bp [18,34]. As a result, we discovered, in silico, two distinct families of fiber conformations (T2 and T1) characterized by different DNA topologies.…”

Section: Topological Polymorphism Of Chromatin Fibersmentioning

confidence: 99%

“…In fact, the average linking number is defined by nucleosome spacing and varies at least from -0.9 to -1.4. (According to computations [18,34] DLk varies from -0.8 to -1.7 in the energetically feasible conformations.) The value DLk = -1.26 measured for the yeast minichromosomes by Roca et al [27] fits in this interval and reflects the average DLk for those configurations of the relatively short nucleosome chains that were stabilized under the experimental conditions.…”

Section: Topological Polymorphism Of Chromatin Fibersmentioning

confidence: 99%

“…Since the T1 and T2 topoisomers are characterized by distinct linker lengths, {10n+5} and {10n}, respectively, we expected to see a difference in the distribution of sizes of inter-nucleosome linkers in the highly and lowly expressed genes. To verify this assumption, we compared the nucleosome positions in the yeast genes from the top and bottom 25% of the expression level scale [34]. Indeed, the two sets of genes were found to have different distributions of nucleosome repeats: for the highly expressed genes NRL ≈ 161 bp (the average linker length <L> = 14 bp), and for the lowly expressed genes NRL ≈ 167 bp (<L> = 20 bp).…”

Section: Nucleosome Spacing and The Level Of Transcriptionmentioning

confidence: 99%

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Polymorphic 30-nm Chromatin Fiber and Linking Number Paradox. Evidence for the Occurrence of Two Distinct Topoisomers

Norouzi

Zhurkin

2018

Preprint

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We discuss various models of spatial organization of the 30-nm fiber that remains enigmatic despite 40 years of intensive studies. Using computer simulations, we found two topologically different families of the fiber conformations distinguished by the linker length, L: the fibers with L = {10n} and {10n+5} bp have DNA linking numbers per nucleosome DLk » -1.5 and -1.0, respectively. The fibers with DLk » -1.5 were observed earlier, while the topoisomer with DLk » -1.0 is novel. These predictions were confirmed for circular nucleosome arrays with precisely positioned nucleosomes. We suggest that topological polymorphism of chromatin fibers may play a role in the process of transcription, which is known to generate different levels of DNA supercoiling upstream and downstream from RNA polymerase. In particular, the {10n+5} DNA linkers are likely to produce transcriptionally competent chromatin structures. This hypothesis is consistent with available data for several eukaryotes, from yeast to human. We also analyzed two recent studies of chromatin fibers -on the nucleosome crosslinking in vitro, and on radioprobing DNA folding in human cells. In both cases, we show that the novel topoisomer with DLk » -1.0 has to be taken into account to interpret experimental data. This is yet another evidence for occurrence of two distinct fiber topoisomers. Potentially, our findings may reflect a general tendency of chromosomal domains with different levels of transcription to retain topologically different higher-order structures.

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“…We obtained this result rigorously [18,34], evaluating the Wr and DLk values through calculations of the Gauss double integral [41,42]. At the qualitative level, it is illustrated in Fig.…”

Section: Topological Polymorphism Of Chromatin Fibersmentioning

confidence: 92%

Section: Topological Polymorphism Of Chromatin Fibersmentioning

confidence: 98%

Section: Topological Polymorphism Of Chromatin Fibersmentioning

confidence: 99%

Section: Topological Polymorphism Of Chromatin Fibersmentioning

confidence: 99%

Section: Nucleosome Spacing and The Level Of Transcriptionmentioning

confidence: 99%

See 3 more Smart Citations

Polymorphic 30-nm Chromatin Fiber and Linking Number Paradox. Evidence for the Occurrence of Two Distinct Topoisomers

Norouzi

Zhurkin

2018

Preprint

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Kilobase Pair Chromatin Fiber Contacts Promoted by Living-System-Like DNA Linker Length Distributions and Nucleosome Depletion

2017

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Nucleosome placement, or DNA linker length patterns, are believed to yield specific spatial features in chromatin fibers, but details are unknown. Here we examine by mesoscale modeling how kilobase (kb) range contacts and fiber looping depend on linker lengths ranging from 18–45 bp, with values modeled after living systems, including Nucleosome Free Regions (NFRs) and gene encoding segments. We also compare artificial constructs with alternating versus randomly distributed linker lengths in the range of 18–72 bp. We show that non-uniform distributions with NFRs enhance flexibility and encourage kb-range contacts. NFRs between neighboring gene segments diminish short-range contacts between flanking nucleosomes, while enhancing kb range contacts via hierarchical looping. We also demonstrate that variances in linker lengths enhance kb range contacts. In particular, moderate sized variations in fiber linker lengths (∼27 bp) encourage long range contacts in randomly distributed linker length fibers. Our work underscores the importance of linker length patterns in biological regulation. Contacts formed by kb-range chromatin folding are crucial to gene activity. Because we find that special linker length distributions in living systems promote kb contacts, these patterns together with bound proteins, are crucial to regulation of gene activity.

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Braiding topology and the energy landscape of chromosome organization proteins

Krepel

Davtyan

Schafer

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Assemblies of structural maintenance of chromosomes (SMC) proteins and kleisin subunits are essential to chromosome organization and segregation across all kingdoms of life. While structural data exist for parts of the SMC−kleisin complexes, complete structures of the entire complexes have yet to be determined, making mechanistic studies difficult. Using an integrative approach that combines crystallographic structural information about the globular subdomains, along with coevolutionary information and an energy landscape optimized force field (AWSEM), we predict atomic-scale structures for several tripartite SMC−kleisin complexes, including prokaryotic condensin, eukaryotic cohesin, and eukaryotic condensin. The molecular dynamics simulations of the SMC−kleisin protein complexes suggest that these complexes exist as a broad conformational ensemble that is made up of different topological isomers. The simulations suggest a critical role for the SMC coiled-coil regions, where the coils intertwine with various linking numbers. The twist and writhe of these braided coils are coupled with the motion of the SMC head domains, suggesting that the complexes may function as topological motors. Opening, closing, and translation along the DNA of the SMC−kleisin protein complexes would allow these motors to couple to the topology of DNA when DNA is entwined with the braided coils.

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Topological Diversity of Chromatin Fibers: Interplay Between Nucleosome Repeat Length, DNA Linking Number and the Level of Transcription

Cited by 9 publications

References 0 publications

Polymorphic 30-nm Chromatin Fiber and Linking Number Paradox. Evidence for the Occurrence of Two Distinct Topoisomers

Polymorphic 30-nm Chromatin Fiber and Linking Number Paradox. Evidence for the Occurrence of Two Distinct Topoisomers

Kilobase Pair Chromatin Fiber Contacts Promoted by Living-System-Like DNA Linker Length Distributions and Nucleosome Depletion

Braiding topology and the energy landscape of chromosome organization proteins

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