Solution structure of the isolated histone H2A-H2B heterodimer

Moriwaki, Yoshihito; Yamane, Tsutomu; Ohtomo, Hideaki; Ikeguchi, Mitsunori; Kurita, Jun; Sato, Masahiko; Nagadoi, Aritaka; Shimojo, Hideaki; Nishimura, Yoshifumi

doi:10.1038/srep24999

Cited by 34 publications

(38 citation statements)

References 39 publications

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“…Removal of a histone dimer has little influence on the secondary structure of other remaining histone proteins. On the other hand, α-helix formation was occasionally observed in histone tail residues; which agrees with previous reports suggesting that histone-tail regions show transient α-helix formation when interacting with DNA (25,26).…”

Section: Structures Of Histone Proteinssupporting

confidence: 92%

Histone Tail Dynamics in Partially Disassembled Nucleosomes During Chromatin Remodeling

Kameda

Awazu

Togashi

2019

Preprint

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Nucleosomes are structural units of the chromosome consisting of DNA wrapped around histone proteins, and play important roles in compaction and regulation of the chromatin structure. While the structure and dynamics of canonical nucleosomes have been studied extensively, those of nucleosomes in intermediate states, that occur when their structure or positioning is modulated, have been less understood. In particular, the dynamic features of partially disassembled nucleosomes have not been discussed in previous studies. Using all-atom molecular dynamics simulations, in this study, we investigated the dynamics and stability of nucleosome structures lacking a histone-dimer. DNA in nucleosomes lacking a histone H2A/H2B dimer was drastically deformed due to loss of local interactions between DNA and histones. In contrast, conformation of DNA in nucleosomes lacking H3/H4 was similar to the canonical nucleosome, as the H2A C-terminal domain infiltrated the space originally occupied by the dissociated H3/H4 histones and stabilized DNA in close proximity. Our results suggest that, besides histone chaperones, the intrinsic dynamics of nucleosomes support the exchange of H2A/H2B, which is significantly more frequent than that of H3/H4. Statement of SignificanceEukaryotic chromosomes are composed of nucleosomes, in which the DNA wraps around the core histone proteins. To enable transcription and replication of DNA, or to modulate these functions by exchange of histones, nucleosomes should be at least partially disassembled, as evidenced by the observation of nucleosome structures lacking an H2A/H2B histone dimer by crystallography. The dynamic behavior of nucleosomes in such intermediate states may affect gene expression and repair, however it has not been completely elucidated so far. In this study, we adopted molecular dynamics simulations to analyze the conformational changes in partially disassembled nucleosomes. Enhanced structural fluctuations of DNA were observed in these nucleosomes, which may, as well as specific histone chaperones, support the exchange of H2A/H2B.

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Section: Structures Of Histone Proteinssupporting

confidence: 92%

Histone Tail Dynamics in Partially Disassembled Nucleosomes During Chromatin Remodeling

Kameda

Awazu

Togashi

2019

Preprint

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“…This slight alteration in the nucleosome could potentially affect binding of proteins that recognize nucleosomal surface features. Furthermore, since the αN helix of H2A stabilizes the αC helix of H2B in the nucleosome, and additionally, is involved in hydrogen bonding to DNA, the amino acid substitutions in this region can affect the stability of the H2A–H2B dimer ( 58 ).…”

Section: Discussionmentioning

confidence: 99%

Replication-dependent histone isoforms: a new source of complexity in chromatin structure and function

Singh

Bassett

Chakravarti

et al. 2018

Nucleic Acids Research

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Replication-dependent histones are expressed in a cell cycle regulated manner and supply the histones necessary to support DNA replication. In mammals, the replication-dependent histones are encoded by a family of genes that are located in several clusters. In humans, these include 16 genes for histone H2A, 22 genes for histone H2B, 14 genes for histone H3, 14 genes for histone H4 and 6 genes for histone H1. While the proteins encoded by these genes are highly similar, they are not identical. For many years, these genes were thought to encode functionally equivalent histone proteins. However, several lines of evidence have emerged that suggest that the replication-dependent histone genes can have specific functions and may constitute a novel layer of chromatin regulation. This Survey and Summary reviews the literature on replication-dependent histone isoforms and discusses potential mechanisms by which the small variations in primary sequence between the isoforms can alter chromatin function. In addition, we summarize the wealth of data implicating altered regulation of histone isoform expression in cancer.

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“…Notably, the αN helix of H2A is not apparent in a recent NMR solution structure of the human H2A/H2B dimer 24 . In the structure of the nucleosome, the H2A αN makes direct contacts with the phosphate backbone of DNA and is likely stabilized by these contacts.…”

Section: Resultsmentioning

confidence: 94%

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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Solution structure of the isolated histone H2A-H2B heterodimer

Cited by 34 publications

References 39 publications

Histone Tail Dynamics in Partially Disassembled Nucleosomes During Chromatin Remodeling

Histone Tail Dynamics in Partially Disassembled Nucleosomes During Chromatin Remodeling

Replication-dependent histone isoforms: a new source of complexity in chromatin structure and function

Structure of a Single Chain H2A/H2B Dimer

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