Linker DNA bending induced by the core histones of chromatin

Yao, Jiaqi; Lowary, Peggy T.; Widom, Jonathan

doi:10.1021/bi00098a019

Cited by 69 publications

(51 citation statements)

References 44 publications

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“…This, however, does not eliminate the mixed straight/bent linker conformation as it is supported by simultaneous presence of i Ϯ 1 and i Ϯ 2 interactions in chromatin fibers condensed by 4 mM Mg 2ϩ . The resulting oligonucleosomes with mostly straight but some bent linker DNAs reconcile apparently contradictory evidence for straight (7)(8)(9)(10) or bent (48,49) linker DNA conformations. Such heteromorphic fibers (with straight/bent linker DNA configurations) allow chromatin to achieve higher levels of compaction, because bent linker DNAs require fewer linker DNA crossings in the middle of the fiber and hence reduce electrostatic repulsion between DNA molecules.…”

Section: Discussionsupporting

confidence: 58%

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: Discussionsupporting

confidence: 58%

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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“…D, internucleosomal cross-linking data shown in A-C were quantified as described in Fig. 4C and plotted reflects the salt-dependent folding of nucleosome arrays (27)(28)(29). However we were unable to detect internucleosomal interactions of the H3 tail domain in dinucleosomes.…”

Section: Discussionmentioning

confidence: 99%

Salt-dependent Intra- and Internucleosomal Interactions of the H3 Tail Domain in a Model Oligonucleosomal Array

Zheng

Hansen

et al. 2005

Journal of Biological Chemistry

113

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The core histone tail domains are known to be key regulators of chromatin structure and function. The tails are required for condensation of nucleosome arrays into secondary and tertiary chromatin structures, yet little is known regarding tail structures or sites of tail interactions in chromatin. We have developed a system to test the hypothesis that the tails participate in internucleosomal interactions during salt-dependent chromatin condensation, and here we used it to examine interactions of the H3 tail domain. We found that the H3 tail participates primarily in intranucleosome interactions when the nucleosome array exists in an extended "beads-ona-string" conformation and that tail interactions reorganize to engage in primarily internucleosome interactions as the array successively undergoes salt-dependent folding and oligomerization. These results indicated that the location and interactions of the H3 tail domain are dependent upon the degree of condensation of the nucleosomal array, suggesting a mechanism by which alterations in tail interactions may elaborate different structural and functional states of chromatin.The eukaryotic genome is assembled into vast arrays of nucleosomes, which are in turn condensed into 30-nm chromatin fibers and other secondary chromatin structures (1-3). In vitro evidence indicates that the folding of nucleosome arrays into secondary structures is strongly favored at physiological concentrations of mono-and divalent salts, as is the oligomerization of arrays into higher order, tertiary chromatin structures (2, 4, 5). The stability of secondary and tertiary chromatin structures is influenced by the incorporation of specific non-allelic variants of the core histone proteins, the binding of linker histones, and association of ancillary chromatin proteins (2, 3). It is generally believed that for genomic DNA to be accessible to various enzymatic machineries, the chromatin fiber has to undergo transient decondensation, facilitated by specific posttranslational modifications such as lysine acetylation within the histone tail domains or ATP-dependent chromatin remodeling (6, 7).The core histone tail domains are essential for compaction of oligonucleosome arrays into secondary chromatin structures and for efficient assembly of oligomeric tertiary structures (1, 2, 8 -10). However, the structures and interactions of the histone tail domains and the molecular mechanisms by which they facilitate chromatin compaction remain largely uncharacterized. Evidence indicates that these highly basic domains interact with both protein and DNA targets within chromatin (11-15), and it is generally assumed that the core histone tail domains participate in internucleosomal as well as intranucleosome interactions within condensed chromatin. Indeed, several crystal structures of nucleosome core particles indicate that the tails project away from the main body of the nucleosome to potentially mediate internucleosomal interactions (2,16,17). These interactions may occur in cis, between nucleosomes within...

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“…5). On the other hand, the linker DNA of isolated dinucleosomes does show Hi-independent salt-induced bending, allowing the two nucleosomes to touch (36,37), but not to assume the face-to-face contact expected in a solenoidal fiber. Also, reconstituted nucleosome 12-mers undergo a salt-induced compaction independent of histone Hi and thought to involve the bending of linker DNA (38).…”

Section: Discussionmentioning

confidence: 99%

A chromatin folding model that incorporates linker variability generates fibers resembling the native structures.

Woodcock

Grigoryev

Horowitz

et al. 1993

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

241

230

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The "30-nm" chromatin fibers, as observed in eukaryotic nuclei, are considered a discrete level in a hierarchy of DNA folding. At present, there is considerable debate as to how the nudeosomes and linker DNA are organized within chromatin fibers, and a number of models have been proposed, many of which are based on helical symmetry and imply specific contacts between nucleosomes. However, when observed in nuclei or after isolation, chromatin fibers show considerable structural irregularity. In the present study, chromatin folding is considered solely in terms of the known properties of the nudeosome-linker unit, taking into account the relative rotation between consecutive nucleosomes that results from the helical twist of DNA. Model building based on this premise, and with a constant length of linker DNA between consecutive nucleosomes, results in a family of fiber-and ribbon-like structure. When the linker length between nucleosomes is aflowed to vary, as occurs in nature, fibers showing the types of irregulaity observed in nuclei and in isolated chromatin are created. The potential application of the model in determining the three-dimensional organization of chromatin in which nucleosome positions are known is discussed.The genome of most eukaryotes is complexed with proteins to form chromatin (1). Under low salt conditions in vitro, the complex assumes its simplest conformation and is seen as a beaded chain of 11-nm (diameter) nucleosomes (e.g., ref.2). As the ionic strength of the medium is raised, the nucleosomal chain condenses, eventually forming a compact fiber 30-40 nm in diameter (1-3). These compact fibers observed in isolated chromatin in vitro are presumed to be related to similar structures seen in thin sections of certain types of nuclei such as nucleated erythrocytes (e.g., refs. 4 and 5). X-ray scattering studies of whole cells and nuclei often show 30-to 45-nm reflections that have been interpreted as arising from the center-to-center spacing of compact chromatin fibers (6). These results suggest that the compact chromatin fiber constitutes a distinct level of chromatin organization, especially for transcriptionally inactive chromatin. In this context, the architecture of the fiber would implicitly define the substrate for the regulatory events that lead to chromatin unfolding, a prerequisite for transcription.Attempts to deduce the structure of compact chromatin fibers have resulted in a number of proposals that include both symmetrical and nonsymmetrical arrangements of nucleosomes (reviewed in ref. 7). There is evidence suggesting some degree of symmetry in fiber structure: an intermediate conformation between the nucleosome chain and the compact chromatin fiber is a "zig-zag ribbon" (2) that can display considerable regularity (8), and isolated fibers prepared for electron microscopy contain regions with a limited amount of internal order (2, 3, 9-11). All proposed model structuresThe publication costs of this article were defrayed in part by page charge payment. This article must ...

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Linker DNA bending induced by the core histones of chromatin

Cited by 69 publications

References 44 publications

Evidence for heteromorphic chromatin fibers from analysis of nucleosome interactions

Evidence for heteromorphic chromatin fibers from analysis of nucleosome interactions

Salt-dependent Intra- and Internucleosomal Interactions of the H3 Tail Domain in a Model Oligonucleosomal Array

A chromatin folding model that incorporates linker variability generates fibers resembling the native structures.

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