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Canonical histones (H2A, H2B, H3, and H4) are present in all eukaryotes where they package genomic DNA and participate in numerous cellular processes, such as transcription regulation and DNA repair. In addition to the canonical histones, there are many histone variants, which have different amino acid sequences, possess tissue-specific expression profiles, and function distinctly from the canonical counterparts. A number of histone variants, including both core histones (H2A/H2B/H3/H4) and linker histones (H1/H5), have been identified to date. Htz1 (H2A.Z) and CENP-A (CenH3) are present from yeasts to mammals, and H3.3 is present from Tetrahymena to humans. In addition to the prevalent variants, others like H3.4 (H3t), H2A.Bbd, and TH2B, as well as several H1 variants, are found to be specific to mammals. Among them, H2BFWT, H3.5, H3.X, H3.Y, and H4G are unique to primates (or Hominidae). In this review, we focus on localization and function of primate- or hominidae-specific histone variants. Key words: histone variants, H2BFWT, H3.5, H3.X, H3.Y, H4G. Les histones classiques (H2A, H2B, H3 et H4) sont presentes chez tous les eucaryotes ou elles servent a enrouler l'ADN genomique et participent a de nombreux processus cellulaires tels que la regulation de la transcription et la reparation de l'ADN. En plus des histones classiques, il existe plusieurs autres histones qui different quant a leurs sequences d'acides amines, possedent des profils d'expression specifiques de certains tissus et fonctionnent de maniere distincte par rapport a leurs contreparties classiques. Plusieurs variants de l'histone, incluant tant les histones centrales (H2A/H2B/H3/H4) que celles de liaison (H1/H5), ont ete identifies a ce jour. Htzl (H2A.Z) et CENP-A (CenH3) sont presents des levures jusqu'aux mammiferes, tandis que H3.3 est present du Tetrahymena jusqu'aux humains. En plus de ces variants repandus, d'autres encore comme H3.4 (H3t), H2A.Bbd et TH2B, tout comme plusieurs variants de H1 sont specifiques aux mammiferes. Parmi ceuxci, H2BFWT, H3.5, H3.X, H3.Y et H4G sont uniques aux primates (ou Hominidae). Dans cette synthese, les auteurs se concentrent sur la localisation et la fonction des variants de l'histone specifiques des primates ou des hominides. Mots-cles : variants de l'histone, H2BFWT, H3.5, H3.X, H3.Y, H4G., Telomere-localized and spermatogenesis-specific histone variants, H2BFWT Histone H2B, one of the four canonical histones involved in chromatin formation, has several canonical isoforms (Molden et al. 2015) and two variants: TH2B [...]

During transcription elongation, RNA polymerase has been assumed to attain equilibrium between pre- and post-translocated states rapidly relative to the subsequent catalysis. Under this assumption, recent single-molecule studies proposed a branched Brownian ratchet mechanism that necessitates a putative secondary nucleotide binding site on the enzyme. By challenging individual yeast RNA polymerase II with a nucleosomal barrier, we separately measured the forward and reverse translocation rates. Surprisingly, we found that the forward translocation rate is comparable to the catalysis rate. This finding reveals a linear, non-branched ratchet mechanism for the nucleotide addition cycle in which translocation is one of the rate-limiting steps. We further determined all the major on- and off-pathway kinetic parameters in the elongation cycle. The resulting translocation energy landscape shows that the off-pathway states are favored thermodynamically but not kinetically over the on-pathway states, conferring the enzyme its propensity to pause and furnishing the physical basis for transcriptional regulation. DOI:http://dx.doi.org/10.7554/eLife.00971.001.

Abstract Background Within chromatin, the histone variant H2A.Z plays a role in many diverse nuclear processes including transcription, preventing the spread of heterochromatin and epigenetic transcriptional memory. The molecular mechanisms of how H2A.Z mediates its effects are not entirely understood. However, it is now known that H2A.Z has two protein isoforms in vertebrates, H2A.Z-1 and H2A.Z-2, which are encoded by separate genes and differ by 3 amino acid residues. Results We report that H2A.Z-1 and H2A.Z-2 are expressed across a wide range of human tissues, they are both acetylated at lysine residues within the N-terminal region and they exhibit similar, but nonidentical, distributions within chromatin. Our results suggest that H2A.Z-2 preferentially associates with H3 trimethylated at lysine 4 compared to H2A.Z-1. The phylogenetic analysis of the promoter regions of H2A.Z-1 and H2A.Z-2 indicate that they have evolved separately during vertebrate evolution. Conclusions Our biochemical, gene expression, and phylogenetic data suggest that the H2A.Z-1 and H2A.Z-2 variants function similarly yet they may have acquired a degree of functional independence.

Structural variability within histone families, such as H2A, can be achieved through 2 primary mechanisms: the expression of histone variants and the incorporation of chemical modifications. The histone H2A family contains several variants in addition to the canonical H2A forms. In this review, recent developments in the study of the heteromorphous variants H2A.X, H2A.Z, and macroH2A will be discussed. Particular focus will be given to the post-translational modifications (PTMs) of these variants, including phosphorylation, ubiquitination, acetylation, and methylation. The combination of the newly identified N- and C-terminal tail PTMs expands the multiplicity of roles that the individual H2A variants can perform. It is of additional interest that analogous sites within these different histone variants can be similarly modified. Whether this is a redundant function or a finely tuned one, designed to meet specific needs, remains to be elucidated. Key words: histone variants, H2A.Z, H2A.X, macroH2A, post-translational modifications. La variabilite de structure au sein des familles d'histones, comme la famille H2A, peut etre obtenue grace a deux mecanismes principaux : l'expression de variants d'histones et l'incorporation de modifications chimiques. La famille d'histones H2A comporte plusieurs variants en plus de la forme canonique H2A. Les derniers developpements de l'etude des variants heteromorphes H2AA, H2A.Z et macroH2A seront discutes dans cet article de revue. Une attention particulire sera portee aux modifications post-traductionnelles (MPT) de ces variants, notamment la phosphorylation, fubiquitination, l'acetylation et la methylation. La combinaison de ces modifications post-traductionnelles des extremites N- et C-terminales nouvellement identifiees augmente la multiplicite des roles que ces variants individuels de H2A peuvent jouer. Il est d'un interet supplementaire de constater que les sites analogues au sein de ces differents variants d'histones puissent etre similairement modifies. Il reste a determiner s'il s'agit d'une redondance de fonctions ou plutot d'un controle fin concu pour combler des besoins specifiques. Mots-cles : variants d'histones, H2A.Z, H2A.X, macroH2A, modifications post-traductionnelles. [Traduit par la Redaction], Introduction Post-translational modifications of H2A variants The covalent linkage of different chemical moieties to specific amino acid residues within a protein allows for the post-translational diversification of a single protein [...]

COP10 that interacts with ubiquitin-conjugating enzymes (E2s) in vivo, and can enhance their activity in vitro is demonstrated. It is shown that COP10 forms a complex with UV-damaged DNA-binding protein 1a (DDB1a) and de-ethiolated 1 (DET1), and physically interacts with COP1 and the CSN.