Structure and Dynamics of a 197 bp Nucleosome in Complex with Linker Histone H1

Bednář, Jan; Garcia-Saez, I.; Boopathi, Ramachandran; Cutter, Amber R.; Pápai, Gábor; Reymer, Anna; Syed, Sajad Hussain; Lone, Imtiaz Nisar; Tonchev, Ognyan; Crucifix, Corinne; Menoni, Hervé; Papin, Christophe; Skoufias, Dimitrios A.; Kurumizaka, Hitoshi; Lavery, R.; Hamiche, Ali; Hayes, Jeffrey J.; Schultz, Patrick; Angelov, Dimitar; Petosa, Carlo; Dimitrov, Stéfan

doi:10.1016/j.molcel.2017.05.018

Cited by 95 publications

(264 citation statements)

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“…The completed on-dyad GH1 had an RMSD of 0.33 Å relative to the recently published crystallographic GH1 structure (PDB 5NL0, resolution: 5.4 Å). 34 For simulations of the NCP, the linker histone was deleted.…”

Section: System Constructionmentioning

confidence: 99%

“…These studies are supported by cryo-EM experiments of condensed nucleosome arrays which suggested an off-dyad H1 binding mode. 37 In contrast, in cryo-EM experiments of single nucleosomes, H1 has been observed in the on-dyad binding state, 34 while there is evidence to suggest that off-dyad binding in the cryo-EM map of the 30-nm fiber may be a result of cross-linker effects. 42 Taken together, these experiments paint the picture that linker histones likely bind in an ensemble of on-and off-dyad states, and that the balance of these two conformations is dictated by several factors including the linker histone primary sequence, the chromatosome's stereochemical environment, and greater chromatin architecture.…”

Section: Introductionmentioning

confidence: 98%

“…32 Linker histones primarily bind to the nucleosome in two states. In the "on-dyad" location [33][34][35] the linker histone is centered on the dyad axis (Figure 1 (top)), whereas in the "off-dyad" configuration the histone binds in a DNA groove off the dyad axis [36][37][38] (Figure 1 (bottom)). Variations in the linker histone binding mode may result in differences in the mechanical stability and overall packaging within the greater chromatin architecture, which would naturally affect the accessibility of DNA in nuclear processes.…”

Section: Introductionmentioning

confidence: 99%

“…This is in line with the closed-state being the only conformation observed in chromatosome crystal structures. 33,34,42 However, there is evidence suggesting that linker histones may exist in alternative conformations 50,51 and binding orientations. 50,[52][53][54] Despite these many excellent experimental and computational studies, several questions remain concerning linker histones and their nucleosome binding.…”

Section: Introductionmentioning

confidence: 99%

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Elucidating the Influence of Linker Histone Variants on Chromatosome Dynamics and Energetics

Woods

Weresczczynski

2019

Preprint

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Linker histones are epigentic regulators that bind to nucleosomes and alter chromatin structures and dynamics. Biophysical studies have revealed two binding modes in the linker histone/nucleosome complex, the chromatosome, where the linker histone is either centered on or askew from the dyad axis. Each has been posited to have distinct effects on chromatin, however the molecular and thermodynamic mechanisms that drive them and their dependence on linker histone compositions remain poorly understood. We present molecular dynamics simulations of chromatosomes with two linker histone isoforms, globular H1 (GH1) and H5 (GH5), to determine how their differences influence chromatosome structures, energetics, and dynamics.Results show that both linker histones adopt a single compact conformation in solution. Upon binding, DNA flexibility is reduced and there is increased chromatosome compaction. While both isoforms favor on-dyad binding, the enthalpic benefit is significantly higher for GH5. This suggests that GH5 is more capable of overcoming the large entropic reduction required for on-dyad binding than GH1, which helps rationalize experiments that have consistently demonstrated GH5 in on-dyad states but that show GH1 in both locations.These simulations highlights the thermodynamic basis for different linker histone binding motifs, and details their physical and chemical effects on chromatosomes.

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Section: System Constructionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Elucidating the Influence of Linker Histone Variants on Chromatosome Dynamics and Energetics

Woods

Weresczczynski

2019

Preprint

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“…Nucleosomes are variably spaced, with linker DNA ranging from 20-80bp long. To facilitate compaction of chromatin fibers, linker histones, such as H1, are able to bind nucleosomes and linker DNA at the DNA entry and exit points [5][6][7] .…”

Section: Introductionmentioning

confidence: 99%

Structure of a Single Chain H2A/H2B Dimer

Warren¹,

Bonanno²,

Almo³

et al. 2020

Preprint

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ABSTRACTChromatin is the complex assembly of nucleic acids and proteins that makes up the physiological form of the eukaryotic genome. The nucleosome is the fundamental repeating unit of chromatin, composed of ~147bp of DNA wrapped around a histone octamer formed by two copies of each core histone: H2A, H2B, H3 and H4. Prior to nucleosome assembly, and during histone eviction, histones are typically assembled into soluble H2A/H2B dimers and H3/H4 dimers and tetramers. A multitude of factors interact with soluble histone dimers and tetramers, including chaperones, importins, histone modifying enzymes, and chromatin remodeling enzymes. It is still unclear how many of these proteins recognize soluble histones; therefore, there is a need for new structural tools to study non-nucleosomal histones. Here we created a single-chain, tailless Xenopus H2A/H2B dimer by directly fusing the C-terminus of H2B to the N-terminus of H2A. We show that this construct (termed scH2BH2A) is readily expressed in bacteria and can be purified under non-denaturing conditions. A 1.31Å crystal structure of scH2BH2A shows that it adopts a conformation nearly identical to nucleosomal H2A/H2B. This new tool will facilitate future structural studies of a multitude of H2A/H2B-interacting proteins.

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Epigenetic regulation of replication origin assembly: A role for histone H1 and chromatin remodeling factors

Falbo

Costanzo

2020

BioEssays

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During early embryonic development in several metazoans, accurate DNA replication is ensured by high number of replication origins. This guarantees rapid genome duplication coordinated with fast cell divisions. In Xenopus laevis embryos this program switches to one with a lower number of origins at a developmental stage known as mid-blastula transition (MBT) when cell cycle length increases and gene transcription starts. Consistent with this regulation, somatic nuclei replicate poorly when transferred to eggs, suggesting the existence of an epigenetic memory suppressing replication assembly origins at all available sites. Recently, it was shown that histone H1 imposes a non-permissive chromatin configuration preventing replication origin assembly on somatic nuclei. This somatic state can be erased by SSRP1, a subunit of the FACT complex. Here, we further develop the hypothesis that this novel form of epigenetic memory might impact on different areas of vertebrate biology going from nuclear reprogramming to cancer development.

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Structure and Dynamics of a 197 bp Nucleosome in Complex with Linker Histone H1

Cited by 95 publications

References 0 publications

Elucidating the Influence of Linker Histone Variants on Chromatosome Dynamics and Energetics

Elucidating the Influence of Linker Histone Variants on Chromatosome Dynamics and Energetics

Structure of a Single Chain H2A/H2B Dimer

Epigenetic regulation of replication origin assembly: A role for histone H1 and chromatin remodeling factors

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