Nucleosomes as Control Elements for Accessing the Genome

Dechassa, Mekonnen Lemma; Luger, Karolin

doi:10.1002/9783527639991.ch3

Cited by 6 publications

(12 citation statements)

References 210 publications

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“…Numerous X-ray crystallographic studies show that the overall architecture of the nucleosome is remarkably unaffected by variations in histone sequence, PTMs and DNA sequence (reviewed in REFS 4,24). Nevertheless, crystallographic studies allude to effects on nucleosome stability and/or dynamics.…”

Section: Nucleosome Structure and Stabilitymentioning

confidence: 99%

New insights into nucleosome and chromatin structure: an ordered state or a disordered affair?

Luger

Dechassa

Tremethick

2012

Nat Rev Mol Cell Biol

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637

529

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The compaction of genomic DNA into chromatin has profound implications for the regulation of key processes such as transcription, replication and DNA repair. Nucleosomes, the repeating building blocks of chromatin, vary in the composition of their histone protein components. This is the result of the incorporation of variant histones and post-translational modifications of histone amino acid side chains. The resulting changes in nucleosome structure, stability and dynamics affect the compaction of nucleosomal arrays into higher-order structures. It is becoming clear that chromatin structures are not nearly as uniform and regular as previously assumed. This implies that chromatin structure must also be viewed in the context of specific biological functions.

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Section: Nucleosome Structure and Stabilitymentioning

confidence: 99%

New insights into nucleosome and chromatin structure: an ordered state or a disordered affair?

Luger

Dechassa

Tremethick

2012

Nat Rev Mol Cell Biol

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637

529

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“…The main source of information about the atomistic structure of nucleosome comes from the X-ray studies of nucleosome core particles (NCP) (reviewed in [2]), which consistently yield highly similar structures of histones and DNA irrespective of histone sequence variants, mutations, post-translational modifications, DNA sequence, or presence of nucleosome binding proteins, peptides or chemical agents. For example, a superposition of different nucleosome structures using VAST+ algorithm [3] showed very small RMSD deviations of about 1 Å for the aligned parts of histone core regions.…”

Section: Introductionmentioning

confidence: 99%

Coupling between Histone Conformations and DNA Geometry in Nucleosomes on a Microsecond Timescale: Atomistic Insights into Nucleosome Functions

Shaytan

Армеев

Goncearenco

et al. 2016

Journal of Molecular Biology

141

152

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An octamer of histone proteins wraps about 200 base pairs of DNA into two super-helical turns to form nucleosomes found in chromatin. Although the static structure of the nucleosomal core particle has been solved, details of the dynamic interactions between histones and DNA remain elusive. We performed extensively long unconstrained, all-atom microsecond molecular dynamics simulations of nucleosomes including linker DNA segments and full-length histones in explicit solvent. For the first time we were able to identify and characterize the rearrangements in nucleosomes on a microsecond timescale including the coupling between the conformation of the histone tails and the DNA geometry. We found that certain histone tail conformations promoted DNA bulging near its entry/exit sites, resulting in the formation of twist-defects within the DNA. This led to a reorganization of histone-DNA interactions, suggestive of the formation of initial nucleosome sliding intermediates. We characterized the dynamics of the histone tails upon their condensation on the core and linker DNA and showed that tails may adopt conformationally constrained positions due to the insertion of “anchoring” lysines and arginines into the DNA minor grooves. Potentially, these phenomena affect the accessibility of post-translationally modified histone residues which serve as important sites for epigenetic marks (e.g. at H3K9, H3K27, H4K16), suggesting that interactions of the histone tails with the core and linker DNA modulate the processes of histone tail modifications and binding of the effector proteins. We discuss the implications of the observed results on the nucleosome function and compare our results to different experimental studies.

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“…Nucleosome positioning with respect to genomic sequence is sensitive to many intrinsic and external factors ( Tsankov et al, 2011 ; West et al, 2014 ), especially in euchromatin, where positioning is dynamic and responsive to cellular identity and internal nuclear environment ( Hughes et al, 2012 ). Gene activation is facilitated by DNA and nucleosome thermodynamics, the nucleosomal surface and chromatin higher order structure ( Dechassa and Luger, 2012 ). Thus initiation and progress of transcription is dependent upon RNA polymerase II (RNA Pol II) gaining access to DNA wrapped around nucleosomes, by harnessing fluctuations that locally unwrap DNA, rather than unwrapping nucleosomes ( Mack et al, 2012 ).…”

Section: Chromatin Architecture and Dynamicsmentioning

confidence: 99%

“…The complimentary roles of 5mC and H2A.Z associated with nucleosome stability may also be based on their respective biophysical and thermodynamic properties. H2A.Z has been shown to contribute to increased nucleosome stability compared with the canonical H2A, with structural and thermodynamic evidence for a more stable interface via the extended acidic path of the H2A.Z dimer and the charged tails of the (H3–H4) 2 tetramer ( Dechassa and Luger, 2012 ). These differences in electrostatic potential and size affect the interface with neighboring nucleosomes and other nuclear proteins ( Chakravarthy et al, 2005 ), and can also contribute to compaction of the 30 nM fiber ( Fan et al, 2002 ).…”

Section: Epigenetic Modifications Modify Chromatin Architecturementioning

confidence: 99%

Crop epigenetics and the molecular hardware of genotype × environment interactions

King

2015

Front. Plant Sci.

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Crop plants encounter thermal environments which fluctuate on a diurnal and seasonal basis. Future climate resilient cultivars will need to respond to thermal profiles reflecting more variable conditions, and harness plasticity that involves regulation of epigenetic processes and complex genomic regulatory networks. Compartmentalization within plant cells insulates the genomic central processing unit within the interphase nucleus. This review addresses the properties of the chromatin hardware in which the genome is embedded, focusing on the biophysical and thermodynamic properties of DNA, histones and nucleosomes. It explores the consequences of thermal and ionic variation on the biophysical behavior of epigenetic marks such as DNA cytosine methylation (5mC), and histone variants such as H2A.Z, and how these contribute to maintenance of chromatin integrity in the nucleus, while enabling specific subsets of genes to be regulated. Information is drawn from theoretical molecular in vitro studies as well as model and crop plants and incorporates recent insights into the role epigenetic processes play in mediating between environmental signals and genomic regulation. A preliminary speculative framework is outlined, based on the evidence of what appears to be a cohesive set of interactions at molecular, biophysical and electrostatic level between the various components contributing to chromatin conformation and dynamics. It proposes that within plant nuclei, general and localized ionic homeostasis plays an important role in maintaining chromatin conformation, whilst maintaining complex genomic regulation that involves specific patterns of epigenetic marks. More generally, reversible changes in DNA methylation appear to be consistent with the ability of nuclear chromatin to manage variation in external ionic and temperature environment. Whilst tentative, this framework provides scope to develop experimental approaches to understand in greater detail the internal environment of plant nuclei. It is hoped that this will generate a deeper understanding of the molecular mechanisms underlying genotype × environment interactions that may be beneficial for long-term improvement of crop performance in less predictable climates.

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Nucleosomes as Control Elements for Accessing the Genome

Cited by 6 publications

References 210 publications

New insights into nucleosome and chromatin structure: an ordered state or a disordered affair?

New insights into nucleosome and chromatin structure: an ordered state or a disordered affair?

Coupling between Histone Conformations and DNA Geometry in Nucleosomes on a Microsecond Timescale: Atomistic Insights into Nucleosome Functions

Crop epigenetics and the molecular hardware of genotype × environment interactions

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