Higher-Order Structures of Chromatin: The Elusive 30 nm Fiber

Tremethick, David J.

doi:10.1016/j.cell.2007.02.008

Cited by 306 publications

(253 citation statements)

References 21 publications

(32 reference statements)

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“…NCPs are flanked by linker DNA, and NCP repeats are folded into the 10 nm chromatin fiber. Linker histone H1 seals the entry and exit of nucleosomal DNA and is involved in folding and stabilization of the 30 nm chromatin fiber (Tremethick, 2007).…”

Section: Introductionmentioning

confidence: 99%

Role of Template Activating Factor-I as a chaperone in linker histone dynamics

Kato

Okuwaki

Nagata

2011

Journal of Cell Science

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SummaryLinker histone H1 is a fundamental chromosomal protein involved in the maintenance of higher-ordered chromatin organization. The exchange dynamics of histone H1 correlates well with chromatin plasticity. A variety of core histone chaperones involved in core histone dynamics has been identified, but the identity of the linker histone chaperone in the somatic cell nucleus has been a longstanding unanswered question. Here we show that Template Activating Factor-I (TAF-I, also known as protein SET) is involved in histone H1 dynamics as a linker histone chaperone. Among previously identified core histone chaperones and linker histone chaperone candidates, only TAF-I was found to be associated specifically with histone H1 in mammalian somatic cell nuclei. TAF-I showed linker histone chaperone activity in vitro. Fluorescence recovery after photobleaching analyses revealed that TAF-I is involved in the regulation of histone H1 dynamics in the nucleus. Therefore, we propose that TAF-I is a key molecule that regulates linker histonemediated chromatin assembly and disassembly.

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Section: Introductionmentioning

confidence: 99%

Role of Template Activating Factor-I as a chaperone in linker histone dynamics

Kato

Okuwaki

Nagata

2011

Journal of Cell Science

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“…Despite this fundamental knowledge, the resolution of the electron micrographs was not sufficient to visualize the organization of the individual nucleosomes within the compact 30-nm fiber. Thus the nucleosome arrangement within the fiber, and accordingly the interpretation of basic chromatin functions, was based on indirect methods, leading to various models, which have hitherto been disputed (9).…”

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confidence: 99%

Evidence for short-range helical order in the 30-nm chromatin fibers of erythrocyte nuclei

Scheffer

Eltsov

Frangakis

2011

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

139

122

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Chromatin folding in eukaryotes fits the genome into the limited volume of the cell nucleus. Formation of higher-order chromatin structures attenuates DNA accessibility, thus contributing to the control of essential genome functions such as transcription, DNA replication, and repair. The 30-nm fiber is thought to be the first hierarchical level of chromatin folding, but the nucleosome arrangement in the compact 30-nm fiber was previously unknown. We used cryoelectron tomography of vitreous sections to determine the structure of the compact, native 30-nm fiber of avian erythrocyte nuclei. The predominant geometry of the 30-nm fiber revealed by subtomogram averaging is a left-handed two-start helix with approximately 6.5 nucleosomes per 11 nm, in which the nucleosomes are juxtaposed face-to-face but are shifted off their superhelical axes with an axial translation of approximately 3.4 nm and an azimuthal rotation of approximately 54°. The nucleosomes produce a checkerboard pattern when observed in the direction perpendicular to the fiber axis but are not interdigitated. The nucleosome packing within the fibers shows larger center-to-center internucleosomal distances than previously anticipated, thus excluding the possibility of core-to-core interactions, explaining how transcription and regulation factors can access nucleosomes.

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“…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)(4)(5)(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.…”

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

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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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Higher-Order Structures of Chromatin: The Elusive 30 nm Fiber

Abstract: Despite progress in understanding chromatin function, the structure of the 30 nm chromatin fiber has remained elusive. However, with the recent crystal structure of a short tetranucleosomal array, the 30 nm fiber is beginning to come into view.

Cited by 306 publications

References 21 publications

Role of Template Activating Factor-I as a chaperone in linker histone dynamics

Role of Template Activating Factor-I as a chaperone in linker histone dynamics

Evidence for short-range helical order in the 30-nm chromatin fibers of erythrocyte nuclei

Evidence for heteromorphic chromatin fibers from analysis of nucleosome interactions

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