Histone Variant H2A.L.2 Guides Transition Protein-Dependent Protamine Assembly in Male Germ Cells

Barral, Sophie; Morozumi, Yuichi; Tanaka, H.; Montellier, Emilie; Govin, Jérôme; Dieuleveult, Maud de; Charbonnier, Guillaume; Couté, Yohann; Puthier, Denis; Buchou, Thierry; Boussouar, Fayçal; Urahama, Takashi; Fenaille, François; Curtet, Sandrine; Héry, Patrick; Fernandez-Nunez, Nicolas; Shiota, Hitoshi; Gérard, Matthieu; Rousseaux, Sophie; Kurumizaka, Hitoshi; Khochbin, Saadi

doi:10.1016/j.molcel.2017.02.025

Cited by 121 publications

(164 citation statements)

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“…This idea is supported by structural data showing that histone variants alter nucleosome properties (3,8–18). Some histone variants evolved only amongst specific taxa, such as testicular H3 in mammals (19,20), sperm specific variants in plants (21), H2A.W in land plants (22), macroH2A in metazoans (23), H2A.L and H2A.B in mammals (24) and sperm specific variants H2A.Q and H2A.R in mammals (25). …”

Section: Introductionmentioning

confidence: 99%

Histone H2A variants confer specific properties to nucleosomes and impact on chromatin accessibility

Osakabe

Lorković

Kobayashi

et al. 2018

Nucleic Acids Research

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In eukaryotes, variants of core histone H2A are selectively incorporated in distinct functional domains of chromatin and are distinguished by conserved sequences of their C-terminal tail, the L1 loop and the docking domain, suggesting that each variant confers specific properties to the nucleosome. Chromatin of flowering plants contains four types of H2A variants, which biochemical properties have not been characterized. We report that in contrast with animals, in Arabidopsis thaliana H2A variants define only four major types of homotypic nucleosomes containing exclusively H2A, H2A.Z, H2A.X or H2A.W. In vitro assays show that the L1 loop and the docking domain confer distinct stability of the nucleosome. In vivo and in vitro assays suggest that the L1 loop and the docking domain cooperate with the C-terminal tail to regulate chromatin accessibility. Based on these findings we conclude that the type of H2A variant in the nucleosome impacts on its interaction with DNA and propose that H2A variants regulate the dynamics of chromatin accessibility. In plants, the predominance of homotypic nucleosomes with specific physical properties and their specific localization to distinct domains suggest that H2A variants play a dominant role in chromatin dynamics and function.

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Section: Introductionmentioning

confidence: 99%

Histone H2A variants confer specific properties to nucleosomes and impact on chromatin accessibility

Osakabe

Lorković

Kobayashi

et al. 2018

Nucleic Acids Research

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“…Based on this feature, H2A.B was previously also referred to as H2A.Lap1 for "lack of acidic patch" (Soboleva, et al 2012). Consequently, nucleosomes containing short H2A variants wrap shorter stretches of DNA (~120-130bp) than canonical H2A-containing nucleosomes (~150bp) and form more loosely-packed, labile chromatin in vitro (Angelov, et al 2004;Gautier, et al 2004;Doyen, et al 2006;Syed, et al 2009;Soboleva, et al 2012;Arimura, et al 2013) and in vivo (Govin, et al 2007;Barral, et al 2017;).…”

Section: Introductionmentioning

confidence: 99%

Evolutionary origins and diversification of testis-specific short histone H2A variants in mammals

Molaro

Young

Malik

2017

Preprint

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Eukaryotic genomes must accomplish the tradeoff between compact packaging for genome stability and inheritance, and accessibility for gene expression. They do so using post-translational modifications of four ancient canonical histone proteins (H2A, H2B, H3 and H4), and by deploying histone variants with specialized chromatin functions. While some histone variants are highly conserved across eukaryotes, others carry out lineage-specific functions. Here, we characterize the evolution of male germline-specific "short H2A variants", which wrap shorter DNA fragments than canonical H2A. In addition to three previously described H2A.B, H2A.L and H2A.P variants, we describe a novel, extremely short H2A histone variant: H2A.Q. We show that H2A.B, H2A.L, H2A.P and H2A.Q are most closely related to a novel, more canonical mmH2A variant found only in monotremes and marsupials. Using phylogenomics, we trace the origins and early diversification of short histone variants into four distinct clades to the ancestral X chromosome of placental mammals. We show that short H2A variants further diversified by repeated lineage-specific amplifications and losses, including pseudogenization of H2A.L in many primates. We also uncover evidence for concerted evolution of H2A.B and H2A.L genes by gene conversion in many species, involving loci separated by large distances. Finally, we find that short H2As evolve more rapidly than any other histone variant, with evidence that positive selection has acted upon H2A.P in primates. Based on their X chromosomal location and pattern of genetic innovation, we speculate that short H2A histone variants are engaged in a form of genetic conflict involving the mammalian sex chromosomes. IntroductionNucleosomes are the basic unit of chromatin in practically all eukaryotes. A typical nucleosome particle wraps 150bp of DNA around an octamer of four histone proteins: H3, H4, H2A and H2B (Kornberg 1974;Kornberg and Thomas 1974;Malik and Henikoff 2003). These four canonical "core" histone proteins have a stereotypical structure characterized by alpha-helices comprising a "histone fold domain" (HFD) (Luger, et al. 1997). During nucleosome assembly, the HFD mediates dimerization of H3 with H4, and that of H2A with H2B, and contains the nucleosome-DNA interface. Nucleosomes thus comprise a central core of a H3-H4 tetramer, flanked by two H2A-H2B dimers. In contrast to their HFD, the N-and C-terminal tails of canonical histones are far less structured and remain solvent-exposed in the nucleosome.. CC-BY-NC 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/165936 doi: bioRxiv preprint first posted online Jul. 20, 2017; 3 Nucleosomes can prevent other cellular factors, such as transcription factors, from interacting with DNA. While the post-translational modification of histone tails play an important role in regulating these interactions, eukaryotic genomes also establish diverse chroma...

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“…Taken together, we conclude that the PSMA8 deficiency causes a delay during the meiotic divisions with a relative accumulation of spermatocytes at metaphase I/II and that the resulting round spermatids enter apoptosis soon after their formation, leading to nonobstructive azoospermia (NOA) and consequently to infertility. We verified the arrest by lack of immunolabelling with TNP1 and TNP2 ( Fig EV3A-B), two transition proteins involved in the replacement of histones by protamines at later stages of spermiogenesis (Barral et al, 2017). We also analysed the presence of H2AL2 (absent from mutant spermatids, see Fig EV3C), a transition histone essential for the first replacement of histones by TNP1 and TNP2 before protamine incorporation (Barral et al, 2017).…”

Section: Mice Lacking Psma8 Are Infertilementioning

confidence: 79%

“…We verified the arrest by lack of immunolabelling with TNP1 and TNP2 ( Fig EV3A-B), two transition proteins involved in the replacement of histones by protamines at later stages of spermiogenesis (Barral et al, 2017). We also analysed the presence of H2AL2 (absent from mutant spermatids, see Fig EV3C), a transition histone essential for the first replacement of histones by TNP1 and TNP2 before protamine incorporation (Barral et al, 2017).…”

Section: Mice Lacking Psma8 Are Infertilementioning

confidence: 79%

Spermatoproteasome-deficient mice are proficient in meiotic DNA repair but defective in meiotic exit

Gómez-H

Felipe‐Medina²,

et al. 2018

Preprint

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Meiotic recombination generates crossovers which are essential to ensure genome haploidization. The ubiquitin proteasome system regulates meiotic recombination through its association to the synaptonemal complex, a 'zipper'-like structure that holds homologs and provides the structural framework for meiotic recombination. Here we show that the testisspecific α4s subunit (PSMA8) of the spermatoproteasome is located at the synaptonemal complex and is essential for the assembly of its activator PA200. Accordingly, synapsisdeficient mice show delocalization of PSMA8 from the synaptonemal complex. Genetic analysis of Psma8-deficient mice shows normal meiotic DNA repair, crossing over formation and an increase of spermatocytes at metaphase I and metaphase II which either enter into apoptosis or slip to give rise to an early spermatid arrest and infertility. Thus, spermatoproteasome-dependent histone degradation is dispensable for meiotic recombination. We show that PSMA8 deficiency alters the proteostasis of several key meiotic players such as acetylated histones, SYCP3, SYCP1, CDK1 and TRIP13 which in turn leads to an aberrant meiotic exit and early spermatid arrest prior to the histone displacement process that take place subsequently.

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Histone Variant H2A.L.2 Guides Transition Protein-Dependent Protamine Assembly in Male Germ Cells

Cited by 121 publications

References 35 publications

Histone H2A variants confer specific properties to nucleosomes and impact on chromatin accessibility

Histone H2A variants confer specific properties to nucleosomes and impact on chromatin accessibility

Evolutionary origins and diversification of testis-specific short histone H2A variants in mammals

Spermatoproteasome-deficient mice are proficient in meiotic DNA repair but defective in meiotic exit

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