Nucleosome Geometry and Internucleosomal Interactions Control the Chromatin Fiber Conformation

Kepper, Nick; Foethke, Dietrich; Stehr, Rene; Wedemann, Gero; Rippe, Karsten

doi:10.1529/biophysj.107.121079

Cited by 112 publications

(180 citation statements)

References 66 publications

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“…The somewhat smaller compaction values than ϳ10 nucleosmes/11 nm previously reported for chromatin fibers with similar DNA linker length by EM of Mg 2ϩ -compacted chromatin (17) and computational modeling (13,19) are likely because of sampling limitations and neglected internucleosomal interactions [e.g., hydrogen bonding between histone surfaces (40)]. Both our approaches, however, yield a similar (5S) increase in sedimentation constant with Mg 2ϩ ions.…”

Section: Resultsmentioning

confidence: 57%

“…For example, the Rhodes group showed that fiber compaction is both repeat length and linkerhistone dependent (18). Analyses of known structures by the Rippe group (19,20) also suggested the large impact of nucleosome geometry on fiber compaction and the possible role of linker histones in converting between 2 fiber forms. Their systematic Monte Carlo simulations also support the notion that nucleosome interdigitation explains higher order chromatin structure and that the nucleosome repeat length affects the internal structure of the chromatin fiber.…”

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confidence: 99%

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Evidence for heteromorphic chromatin fibers from analysis of nucleosome interactions

Grigoryev

Arya

Correll

et al. 2009

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

245

358

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The architecture of the chromatin fiber, which determines DNA accessibility for transcription and other template-directed biological processes, remains unknown. Here we investigate the internal organization of the 30-nm chromatin fiber, combining Monte Carlo simulations of nucleosome chain folding with EM-assisted nucleosome interaction capture (EMANIC). We show that at physiological concentrations of monovalent ions, linker histones lead to a tight 2-start zigzag dominated by interactions between alternate nucleosomes (i ؎ 2) and sealed by histone N-tails. Divalent ions further compact the fiber by promoting bending in some linker DNAs and hence raising sequential nucleosome interactions (i ؎ 1). Remarkably, both straight and bent linker DNA conformations are retained in the fully compact chromatin fiber as inferred from both EMANIC and modeling. This conformational variability is energetically favorable as it helps accommodate DNA crossings within the fiber axis. Our results thus show that the 2-start zigzag topology and the type of linker DNA bending that defines solenoid models may be simultaneously present in a structurally heteromorphic chromatin fiber with uniform 30 nm diameter. Our data also suggest that dynamic linker DNA bending by linker histones and divalent cations in vivo may mediate the transition between tight nucleosome packing within discrete 30-nm fibers and self-associated higher-order chromosomal forms.chromatin structure ͉ electron microscopy ͉ mesoscopic modeling ͉ Monte Carlo simulations ͉ linker histone T he DNA in eukaryotic chromatin is packed and functionally regulated by histones and nonhistone architectural proteins (1). The primary packing level is represented by an array of repeating units, the nucleosomes, where the DNA is wound around histone octamers (2). Further compaction is achieved through a hierarchy of folding levels, including the 30-nm chromatin fiber (secondary level) and more compact and self-associating tertiary and quaternary forms whose structures are unknown (3-6). Because DNA conformation in chromatin and nucleosome packing are intimately connected to DNA/protein recognition and gene regulation, there has been intense interest in understanding chromatin structure, energetics, and dynamics. Some experimental studies have suggested that nucleosomal arrays fold in a zigzag arrangement with relatively straight linkers and a 2-start nucleosome interaction pattern that brings each nucleosome in proximity to its second nearest neighbor (7-10) consistent with chromatin fibers observed in situ (11). Other evidence suggests that chromatin condensed with linker histones and divalent cations such as Mg 2ϩ can form either zigzag structures with various nucleosome topologies (12, 13) or solenoid-like arrangements. The latter class of structures has bent DNA linkers and predominant interactions between either nearest neighbor nucleosomes (14, 15) and/or between every fifth or sixth nucleosome along the chain (16,17).The picture has became more complex recently with our heighte...

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Section: Resultsmentioning

confidence: 57%

mentioning

confidence: 99%

Evidence for heteromorphic chromatin fibers from analysis of nucleosome interactions

Grigoryev

Arya

Correll

et al. 2009

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

245

358

View full text Add to dashboard Cite

show abstract

“…Unexpectedly, the data revealed a step-wise increase in fiber packing density and diameter. Modeling of these fibers predicted the existence of multi-start fibers with several nucleosome stacks Wong et al 2007;Depken and Schiessel 2009;Kepper et al 2008), but did not provide a uniform explanation for the observed step-wise changes in fiber parameters.…”

Section: -Nm Fibermentioning

confidence: 90%

The regulatory role of DNA supercoiling in nucleoprotein complex assembly and genetic activity

Muskhelishvili

Travers

2016

Biophys Rev

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We argue that dynamic changes in DNA supercoiling in vivo determine both how DNA is packaged and how it is accessed for transcription and for other manipulations such as recombination. In both bacteria and eukaryotes, the principal generators of DNA superhelicity are DNA translocases, supplemented in bacteria by DNA gyrase. By generating gradients of superhelicity upstream and downstream of their site of activity, translocases enable the differential binding of proteins which preferentially interact with respectively more untwisted or more writhed DNA. Such preferences enable, in principle, the sequential binding of different classes of protein and so constitute an essential driver of chromatin organization.Keywords DNA supercoiling . DNA translocases . Chromatin organization . Superhelicity gradients . DNA untwisting . DNAwrithing Dynamic changes of DNA supercoiling act as a driving force behind the alterations of genetic activity and DNA compaction both in eukaryotes and prokaryotes. Both these processes involve formation of spatially organized nucleoprotein structures by DNA architectural proteins. Whereas in eukaryotes the paradigmal example is the histone octamer, in prokaryotes a similar function is attributed to a small class of highly abundant nucleoid-associated proteins. We argue that, depending on the primary sequence organization, the changes of superhelicity elicit various alterations of local DNA geometry, while these, in turn, facilitate the assembly of distinct nucleoprotein structures pertinent to genetic function. Genome-wide conversion of the superhelical energy into various three-dimensional DNA structures thus acts as an analogue code coordinating the energy supply with the genetic expression of the chromosome.Recent studies make it increasingly clear that the DNA double helix carries at least two types of encoded information and that these include the well-known genetic code and the structural information determining the form and physical properties of the double helix itself. Since both these information types are inscribed in the same DNA sequence, and yet one is discrete whereas the other is continuous, they have been respectively dubbed the digital and analog DNA codes (Marr et al. 2008;Travers et al. 2012;Muskhelishvili and Travers 2013). The potential of the DNA to adopt distinct configurations is strongly modulated by DNA supercoiling, which is increasingly recognized as one of the major forces coordinating the cellular DNA transactions in both prokaryotes (including Archaea) and eukaryotes.DNA supercoiling can be generated by the simple application of torque to the double helix (Strick et al. 1998) but, importantly, because the DNA molecule itself possesses chirality-it is, after all, a right-handed double helix-the local structures stabilized by changes in superhelical density depend on both the sign and strength of the applied torque. For example, both positive and negative torque (respectively overand underwinding of the double helix) can change the intrinsic coiling of ...

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“…However, the assumption of uniform interactions between adjacent nucleosomes, such as between the two H2A–H2B dimers seen in the crystal structure 5, results in the dyad axes pointing radially along the nucleosomal stack because each octamer must rotate in the same sense relative to its preceding neighbour. This constraint is typical of the many models that have been proposed for the structure of the compact chromatin fibre 5, 13, 14, 15, 17. Nevertheless, Schalch et al .…”

Section: Relation To Previous Workmentioning

confidence: 96%

“…Unexpectedly the data revealed a step‐wise increase in fibre‐packing density and diameter. Modelling of these fibres predicted the existence of multistart fibres with several nucleosome stacks 14, 15, 16, 17 (Table 1) but did not provide a uniform explanation for the observed step‐wise changes in fibre parameters.…”

Section: Tablementioning

confidence: 97%

A metastable structure for the compact 30‐nm chromatin fibre

McGeehan

Travers

2016

FEBS Letters

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The structure of compact 30‐nm chromatin fibres is still debated. We present here a novel unified model that reconciles all experimental observations into a single framework. We propose that compact fibres are formed by the interdigitation of the two nucleosome stacks in a 2‐start crossed‐linker structure to form a single stack. This process requires that the dyad orientation of successive nucleosomes relative to the helical axis alternates. The model predicts that, as observed experimentally, the fibre‐packing density should increase in a stepwise manner with increasing linker length. This model structure can also incorporate linker DNA of varying lengths.

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Nucleosome Geometry and Internucleosomal Interactions Control the Chromatin Fiber Conformation

Cited by 112 publications

References 66 publications

Evidence for heteromorphic chromatin fibers from analysis of nucleosome interactions

Evidence for heteromorphic chromatin fibers from analysis of nucleosome interactions

The regulatory role of DNA supercoiling in nucleoprotein complex assembly and genetic activity

A metastable structure for the compact 30‐nm chromatin fibre

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