Nucleosome Arrays Reveal the Two-Start Organization of the Chromatin Fiber

Dorigo, Benedetta; Schalch, Thomas; Kulangara, A.; Duda, Sylwia; Schroeder, Rasmus R.; Richmond, Timothy J.

doi:10.1126/science.1103124

Cited by 510 publications

(532 citation statements)

References 20 publications

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“…Recent X-ray studies of crystallized nucleosome arrays (Dorigo et al 2004) and tetranucleosomes (Schalch et al 2005) support this estimate, and suggest that the 30 nm fiber has a two-start helix organization, with linker DNA in the interior of the fiber. This is in accord with neutron scattering experiments on chromatin containing histone H1 which indicate that linker histone is concentrated in the fiber center (Graziano et al 1994).…”

Section: Chromatin Fibrementioning

confidence: 55%

Micromechanical studies of mitotic chromosomes

2008

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Mitotic chromosomes respond elastically to forces in the nanonewton range, a property important to transduction of stresses used as mechanical regulatory signals during cell division. In addition to being important biologically, chromosome elasticity can be used as a tool for investigating the folding of chromatin. This paper reviews experiments studying stretching and bending stiffness of mitotic chromosomes, plus experiments where changes in chromosome elasticity resulting from chemical and enzyme treatments were used to analyse connectivity of chromatin inside chromosomes. Experiments with nucleases indicate that non-DNA elements constraining mitotic chromatin must be isolated from one another, leading to the conclusion that mitotic chromosomes have a chromatin Fnetwork_ or Fgel_ organization, with stretches of chromatin strung between Fcrosslinking_ points. The as-yet unresolved questions of the identities of the putative chromatin crosslinkers and their organization inside mitotic chromosomes are discussed.

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Section: Chromatin Fibrementioning

confidence: 55%

Micromechanical studies of mitotic chromosomes

2008

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“…There is now compelling experimental evidence that the '30-nm' fiber can adopt a 2-start structure. In addition to early EM images (Woodcock et al 1984), a 2-start structure is supported by Fourier analysis of images of chromatin fibers (Williams et al 1986), chemical crosslinking (Dorigo et al 2004), the crystal structure of a tetranucleosome (Schalch et al 2005), cryo-EM of native fibers (Bednar et al 1998), cryo-EM structures of reconstituted fibers containing up to 24 nucleosomes (Song et al 2014), and cryo-tomographic analysis of native chromatin (Horowitz et al 1994;Scheffer et al 2011). Nevertheless, early studies on various native chromatin samples by photochemical dichroism (Sen et al 1986) and X-ray diffraction (Widom and Klug 1985; revealed, respectively, a small tilt of the nucleosomal disc relative to the fiber axis and narrow diffraction arcs at 110 Å.…”

Section: -Nm Fibermentioning

confidence: 99%

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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“…35 A regularly arranged secondary structure known as the "30 nm fiber" is believed to exist. 34,35,39 The organization of this fiber is achieved through two major structures: the "one-start" or solenoid model, in which two successive nucleosomes follow a helical path and are connected by bent linker DNA; or the "two-start" or zig-zag model, in which nucleosomes directly interact with each other with minimal bending of linker DNA between them ( Fig. 2(b)).…”

Section: Challenges In Chromatin Analysismentioning

confidence: 99%

“…27 Since the structure of chromatin itself likely regulates aspects of gene transcription, 28 understanding these factors is of critical importance in probing epigenetics. Intensive research has been conducted to characterize the structural and functional properties of chromatin using diverse experimental and modeling techniques including atomic force microscopy (AFM), [29][30][31] optical/magnetic tweezers, 32,33 electron microscopy, 34,35 and X-ray scattering methods. 36,37 DNA is coiled around a nucleosome core comprising four pairs of histone proteins, and nucleosomes are connected to each other by linker DNA (often represented by a "beads-on-astring" model) ( Fig.…”

Section: Challenges In Chromatin Analysismentioning

confidence: 99%

Micro- and nanofluidic technologies for epigenetic profiling

et al. 2013

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This short review provides an overview of the impact micro- and nanotechnologies can make in studying epigenetic structures. The importance of mapping histone modifications on chromatin prompts us to highlight the complexities and challenges associated with histone mapping, as compared to DNA sequencing. First, the histone code comprised over 30 variations, compared to 4 nucleotides for DNA. Second, whereas DNA can be amplified using polymerase chain reaction, chromatin cannot be amplified, creating challenges in obtaining sufficient material for analysis. Third, while every person has only a single genome, there exist multiple epigenomes in cells of different types and origins. Finally, we summarize existing technologies for performing these types of analyses. Although there are still relatively few examples of micro- and nanofluidic technologies for chromatin analysis, the unique advantages of using such technologies to address inherent challenges in epigenetic studies, such as limited sample material, complex readouts, and the need for high-content screens, make this an area of significant growth and opportunity.

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Nucleosome Arrays Reveal the Two-Start Organization of the Chromatin Fiber

Cited by 510 publications

References 20 publications

Micromechanical studies of mitotic chromosomes

Micromechanical studies of mitotic chromosomes

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

Micro- and nanofluidic technologies for epigenetic profiling

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