Cryo-EM Study of the Chromatin Fiber Reveals a Double Helix Twisted by Tetranucleosomal Units

Song, Feng; Chen, Ping; Sun, Dapeng; Wang, Mingzhu; Dong, Liping; Liang, Dan; Xu, Rui-Ming; Zhu, Ping; Li, Guohong

doi:10.1126/science.1251413

Cited by 530 publications

(822 citation statements)

References 41 publications

(39 reference statements)

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“…In addition to early EM images 3 a 2‐start structure is supported by Fourier analysis of images of chromatin fibres 2, chemical cross‐linking 4, the crystal structure of a tetranucleosome 5, cryo‐EM of native fibres 6, cryo‐EM structures of reconstituted fibres containing up to 24 nucleosomes 7 and cryo‐tomographic analysis of native chromatin 8, 9. Nevertheless, early studies on various native chromatin samples by photochemical dichroism 10 and X‐ray diffraction 11, 12, revealed, respectively, a small tilt of the nucleosomal disc relative to the fibre axis and narrow diffraction arcs at 110 Å.…”

Section: Tablementioning

confidence: 99%

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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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Section: Tablementioning

confidence: 99%

“…Similarly the cryo‐EM structure of Song et al . 7 has a pitch angle of ~ 40°. In contrast, the pitch angle of the merged 2‐start structure is on average ~ 8°.…”

Section: Relation To Previous Workmentioning

confidence: 99%

A metastable structure for the compact 30‐nm chromatin fibre

McGeehan

Travers

2016

FEBS Letters

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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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“…General consensus is that chromatin probably adopts dynamically a mix of structures depending on the cell activity [158,159]. This fluidity helps the cell to modulate chromatin accessibility and accordingly the DNA expression level [158], but complicates the theoretical description of the in vivo chromatin structure.…”

Section: Mesoscopic Studiesmentioning

confidence: 99%

“…Introduction of higher level of detail can be achieved by the intermediate chain-of-beads approach, which involves two features: small-scale chromatin properties and overall genome organization based on experimental results, for example from Hi-C [165], FISH [168] or cryo-EM [159] Hi-C contacts) [171][172][173]. Constant improvement in Hi-C techniques [166] and the recent irruption of ultra-resolution fluorescence microscopy in the field [174] suggests that there is room for th 'int m diat ' a ach t improve thelevel of resolution, with the long-range objective to reach atleastnucleosome-level resolution.…”

Section: Mesoscopic Studiesmentioning

confidence: 99%

Multiscale simulation of DNA

Dans¹,

Walther

Gómez

et al. 2016

Current Opinion in Structural Biology

136

131

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DNA is not only among the most important molecules in life, but a meeting point for biology, physics and chemistry, being studied by numerous techniques. Theoretical methods can help in gaining a detailed understanding of DNA structure and function, but their practical use is hampered by the multiscale nature of this molecule. In this regard, the study of DNA covers a broad range of different topics, from sub-Angstrom details of the electronic distributions of nucleobases, to the mechanical properties of millimeter-long chromatin fibers. Some of the biological processes involving DNA occur in femtoseconds, while others require years. In this review, we describe the most recent theoretical methods that have been considered to study DNA, from the electron to the chromosome, enriching our knowledge on this fascinating molecule.

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Cryo-EM Study of the Chromatin Fiber Reveals a Double Helix Twisted by Tetranucleosomal Units

Cited by 530 publications

References 41 publications

A metastable structure for the compact 30‐nm chromatin fibre

A metastable structure for the compact 30‐nm chromatin fibre

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

Multiscale simulation of DNA

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