Cryo-EM structure of the nucleosome core particle containing <i>Giardia lamblia</i> histones

Sato, Shoko; Takizawa, Yoshimasa; Hoshikawa, Fumika; Dacher, Mariko; Tanaka, H.; Tachiwana, Hiroaki; Kujirai, Tomoya; Iikura, Yukari; Ho, Cheng-Han; Adachi, Naruhiko; Patwal, Indu; Flaus, Andrew; Kurumizaka, Hitoshi

doi:10.1093/nar/gkab644

Cited by 23 publications

(17 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1), the structure exhibits remarkable conservation of overall histone fold architecture. This is consistent with structures from other divergent organisms such as the parasite Giardia lamblia 56 , the archaeon Methanothermus fervidus 57 , or the Marseilleviridae 48,58 giant viruses. However, subtle differences in histone packing and specific histone amino acid substitutions give rise to properties unique to the T. brucei NCP.…”

Section: Discussionsupporting

confidence: 83%

“…2-4). Chromatin arrays constructed from other nucleosomes with DNA end flexibility 46,56,62 were also found to favour more open chromatin conformations, particularly due to alterations in inter-nucleosomal DNA path 62 . Future experiments on chromatin arrays would help explore if entry/exit DNA flexibility described here could explain the more open chromatin in T. brucei.…”

Section: Discussionmentioning

confidence: 96%

See 1 more Smart Citation

Histone divergence inTrypanosoma bruceiresults in unique alterations to nucleosome structure

Deák

Wapenaar

Sandoval

et al. 2023

Preprint

View full text Add to dashboard Cite

Eukaryotes have a multitude of diverse mechanisms for organising and using their genomes, but the histones that make up chromatin are highly conserved. Unusually, histones from kinetoplastids are highly divergent. The structural and functional consequences of this variation are unknown. Here, we have biochemically and structurally characterised nucleosome core particles (NCPs) from the kinetoplastid parasite Trypanosoma brucei. A structure of the T. brucei NCP reveals that global histone architecture is conserved, but specific sequence alterations lead to distinct DNA and protein interaction interfaces. The T. brucei NCP is unstable and has weakened overall DNA binding. However, dramatic changes at the H2A-H2B interface introduce local reinforcement of DNA contacts. The T. brucei acidic patch has altered topology and is refractory to known binders, indicating that the nature of chromatin interactions in T. brucei may be unique. Overall, our results provide a detailed molecular basis for understanding evolutionary divergence in chromatin structure.

show abstract

Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 96%

Histone divergence inTrypanosoma bruceiresults in unique alterations to nucleosome structure

Deák

Wapenaar

Sandoval

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…These observations are in line with recent structural studies of other histone variants. Particularly, Sato et al [ 69 ] have shown that nucleosomes based on histones from G. lamblia demonstrated outward bending of the H2A α2-helix. Concomitantly, Zhou et al [ 33 ] observed that H2A.B-containing nucleosomes had a 15° kink in the C-terminal region of the H2A.B α2-helix, although this kink was more in the direction along the nucleosomal superhelical axis.…”

Section: Discussionmentioning

confidence: 99%

H2A-H2B Histone Dimer Plasticity and Its Functional Implications

Kniazeva

Армеев

Shaytan

2022

Cells

View full text Add to dashboard Cite

The protein core of the nucleosome is composed of an H3-H4 histone tetramer and two H2A-H2B histone dimers. The tetramer organizes the central 60 DNA bp, while H2A-H2B dimers lock the flanking DNA segments. Being positioned at the sides of the nucleosome, H2A-H2B dimers stabilize the overall structure of the nucleosome and modulate its dynamics, such as DNA unwrapping, sliding, etc. Such modulation at the epigenetic level is achieved through post-translational modifications and the incorporation of histone variants. However, the detailed connection between the sequence of H2A-H2B histones and their structure, dynamics and implications for nucleosome functioning remains elusive. In this work, we present a detailed study of H2A-H2B dimer dynamics in the free form and in the context of nucleosomes via atomistic molecular dynamics simulations (based on X. laevis histones). We supplement simulation results by comparative analysis of information in the structural databases. Particularly, we describe a major dynamical mode corresponding to the bending movement of the longest H2A and H2B α-helices. This overall bending dynamics of the H2A-H2B dimer were found to be modulated by its interactions with DNA, H3-H4 tetramer, the presence of DNA twist-defects with nucleosomal DNA and the amino acid sequence of histones. Taken together, our results shed new light on the dynamical mechanisms of nucleosome functioning, such as nucleosome sliding, DNA-unwrapping and their epigenetic modulation.

show abstract

“…The cryo-EM structure of the G. lamblia nucleosome was determined at a 3.6 angstrom resolution, after reconstitution with 145 base pairs of modified Widom 601 (601L) palindromic DNA [ 61 ]. The overall structure of the G. lamblia nucleosome resembles that of the human nucleosome ( Figure 2 A).…”

Section: Structures Of Nucleosomes Containing Parasite Histonesmentioning

confidence: 99%

Nucleosome Structures Built from Highly Divergent Histones: Parasites and Giant DNA Viruses

2022

Self Cite

View full text Add to dashboard Cite

In eukaryotes, genomic DNA is bound with histone proteins and packaged into chromatin. The nucleosome, a fundamental unit of chromatin, regulates the accessibility of DNA to enzymes involved in gene regulation. During the past few years, structural analyses of chromatin architectures have been limited to evolutionarily related organisms. The amino acid sequences of histone proteins are highly conserved from humans to yeasts, but are divergent in the deeply branching protozoan groups, including human parasites that are directly related to human health. Certain large DNA viruses, as well as archaeal organisms, contain distant homologs of eukaryotic histone proteins. The divergent sequences give rise to unique and distinct nucleosome architectures, although the fundamental principles of histone folding and DNA contact are highly conserved. In this article, we review the structures and biophysical properties of nucleosomes containing histones from the human parasites Giardia lamblia and Leishmania major, and histone-like proteins from the Marseilleviridae amoeba virus family. The presented data confirm the sharing of the overall DNA compaction system among evolutionally distant species and clarify the deviations from the species-specific nature of the nucleosome.

show abstract

Cryo-EM structure of the nucleosome core particle containing Giardia lamblia histones

Cited by 23 publications

References 73 publications

Histone divergence inTrypanosoma bruceiresults in unique alterations to nucleosome structure

Histone divergence inTrypanosoma bruceiresults in unique alterations to nucleosome structure

H2A-H2B Histone Dimer Plasticity and Its Functional Implications

Nucleosome Structures Built from Highly Divergent Histones: Parasites and Giant DNA Viruses

Contact Info

Product

Resources

About