Dataset Information

Topological polymorphism of the two-start chromatin fiber.

ABSTRACT: Specific details concerning the spatial organization of nucleosomes in 30 nm fibers remain unknown. To investigate this, we analyzed all stereochemically possible configurations of two-start nucleosome fibers with short DNA linkers L = 13-37 bp (nucleosome repeat length (NRL) = 160-184 bp). Four superhelical parameters-inclination of nucleosomes, twist, rise, and diameter-uniquely describe a regular symmetric fiber. The energy of a fiber is defined as the sum of four terms: elastic energy of the linker DNA, steric repulsion, electrostatics, and a phenomenological (H4 tail-acidic patch) interaction between two stacked nucleosomes. By optimizing the fiber energy with respect to the superhelical parameters, we found two types of topological transition in fibers (associated with the change in inclination angle): one caused by an abrupt 360° change in the linker DNA twisting (change in the DNA linking number, ?Lk = 1), and another caused by overcrossing of the linkers (?Lk = 2). To the best of our knowledge, this topological polymorphism of the two-start fibers was not reported in the computations published earlier. Importantly, the optimal configurations of the fibers with linkers L = 10n and 10n + 5 bp are characterized by different values of the DNA linking number-that is, they are topologically different. Our results are consistent with experimental observations, such as the inclination 60° to 70° (the angle between the nucleosomal disks and the fiber axis), helical rise, diameter, and left-handedness of the fibers. In addition, we make several testable predictions, among them different degrees of DNA supercoiling in fibers with L = 10n and 10n + 5 bp, different flexibility of the two types of fibers, and a correlation between the local NRL and the level of transcription in different parts of the yeast genome.

SUBMITTER: Norouzi D

PROVIDER: S-EPMC4457244 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Topological polymorphism of the two-start chromatin fiber.

Norouzi Davood D Zhurkin Victor B VB

Biophysical journal 20150501 10

Specific details concerning the spatial organization of nucleosomes in 30 nm fibers remain unknown. To investigate this, we analyzed all stereochemically possible configurations of two-start nucleosome fibers with short DNA linkers L = 13-37 bp (nucleosome repeat length (NRL) = 160-184 bp). Four superhelical parameters-inclination of nucleosomes, twist, rise, and diameter-uniquely describe a regular symmetric fiber. The energy of a fiber is defined as the sum of four terms: elastic energy of the ...[more]

PMID: 25992737

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Project description:BACKGROUND:Current Hi-C technologies for chromosome conformation capture allow to understand a broad spectrum of functional interactions between genome elements. Although significant progress has been made into analysis of Hi-C data to identify biologically significant features, many questions still remain open, in particular regarding potential biological significance of various topological features that are characteristic for chromatin interaction networks. RESULTS:It has been previously observed that promoter capture Hi-C (PCHi-C) interaction networks tend to separate easily into well-defined connected components that can be related to certain biological functionality, however, such evidence was based on manual analysis and was limited. Here we present a novel method for analysis of chromatin interaction networks aimed towards identifying characteristic topological features of interaction graphs and confirming their potential significance in chromatin architecture. Our method automatically identifies all connected components with an assigned significance score above a given threshold. These components can be subjected afterwards to different assessment methods for their biological role and/or significance. The method was applied to the largest PCHi-C data set available to date that contains interactions for 17 haematopoietic cell types. The results demonstrate strong evidence of well-pronounced component structure of chromatin interaction networks and provide some characterisation of this component structure. We also performed an indicative assessment of potential biological significance of identified network components with the results confirming that the network components can be related to specific biological functionality. CONCLUSIONS:The obtained results show that the topological structure of chromatin interaction networks can be well described in terms of isolated connected components of the network and that formation of these components can be often explained by biological features of functionally related gene modules. The presented method allows automatic identification of all such components and evaluation of their significance in PCHi-C dataset for 17 haematopoietic cell types. The method can be adapted for exploration of other chromatin interaction data sets that include information about sufficiently large number of different cell types, and, in principle, also for analysis of other kinds of cell type-specific networks.

Dataset Information

Topological polymorphism of the two-start chromatin fiber.

Publications

Topological polymorphism of the two-start chromatin fiber.

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