scholarly journals Short Histone H2A Variants: Small in Stature but not in Function

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 867 ◽  
Author(s):  
Xuanzhao Jiang ◽  
Tatiana A. Soboleva ◽  
David J. Tremethick
Keyword(s):  
Chromatin Structure ◽  
Biochemical Composition ◽  
Histone Variants ◽  
Histone H2a ◽  
The Core ◽  
Unique Protein ◽  
Core Histones ◽  
The Brain ◽  
Fundamental Mechanism ◽  
The Way

The dynamic packaging of DNA into chromatin regulates all aspects of genome function by altering the accessibility of DNA and by providing docking pads to proteins that copy, repair and express the genome. Different epigenetic-based mechanisms have been described that alter the way DNA is organised into chromatin, but one fundamental mechanism alters the biochemical composition of a nucleosome by substituting one or more of the core histones with their variant forms. Of the core histones, the largest number of histone variants belong to the H2A class. The most divergent class is the designated “short H2A variants” (H2A.B, H2A.L, H2A.P and H2A.Q), so termed because they lack a H2A C-terminal tail. These histone variants appeared late in evolution in eutherian mammals and are lineage-specific, being expressed in the testis (and, in the case of H2A.B, also in the brain). To date, most information about the function of these peculiar histone variants has come from studies on the H2A.B and H2A.L family in mice. In this review, we describe their unique protein characteristics, their impact on chromatin structure, and their known functions plus other possible, even non-chromatin, roles in an attempt to understand why these peculiar histone variants evolved in the first place.

scholarly journals Identification and Characterization of the Genes Encoding the Core Histones and Histone Variants of Neurospora crassa

Genetics ◽  
2002 ◽  
Vol 160 (3) ◽  
pp. 961-973 ◽  
Author(s):  
Shan M Hays ◽  
Johanna Swanson ◽  
Eric U Selker
Keyword(s):  
Neurospora Crassa ◽  
Histone Variants ◽  
Null Alleles ◽  
Histone Genes ◽  
Histone H4 ◽  
Coding Regions ◽  
The Core ◽  
Genomic Arrangement ◽  
Genes Encoding ◽  
Core Histones

Abstract We have identified and characterized the complete complement of genes encoding the core histones of Neurospora crassa. In addition to the previously identified pair of genes that encode histones H3 and H4 (hH3 and hH4-1), we identified a second histone H4 gene (hH4-2), a divergently transcribed pair of genes that encode H2A and H2B (hH2A and hH2B), a homolog of the F/Z family of H2A variants (hH2Az), a homolog of the H3 variant CSE4 from Saccharomyces cerevisiae (hH3v), and a highly diverged H4 variant (hH4v) not described in other species. The hH4-1 and hH4-2 genes, which are 96% identical in their coding regions and encode identical proteins, were inactivated independently. Strains with inactivating mutations in either gene were phenotypically wild type, in terms of growth rates and fertility, but the double mutants were inviable. As expected, we were unable to isolate null alleles of hH2A, hH2B, or hH3. The genomic arrangement of the histone and histone variant genes was determined. hH2Az and the hH3-hH4-1 gene pair are on LG IIR, with hH2Az centromere-proximal to hH3-hH4-1 and hH3 centromere-proximal to hH4-1. hH3v and hH4-2 are on LG IIIR with hH3v centromere-proximal to hH4-2. hH4v is on LG IVR and the hH2A-hH2B pair is located immediately right of the LG VII centromere, with hH2A centromere-proximal to hH2B. Except for the centromere-distal gene in the pairs, all of the histone genes are transcribed toward the centromere. Phylogenetic analysis of the N. crassa histone genes places them in the Euascomycota lineage. In contrast to the general case in eukaryotes, histone genes in euascomycetes are few in number and contain introns. This may be a reflection of the evolution of the RIP (repeat-induced point mutation) and MIP (methylation induced premeiotically) processes that detect sizable duplications and silence associated genes.

Histone Variants: The Nexus of Developmental Decisions and Epigenetic Memory

2020 ◽  
Vol 54 (1) ◽  
pp. 121-149 ◽  
Author(s):  
Benjamin Loppin ◽  
Frédéric Berger
Keyword(s):  
Cell Differentiation ◽  
Cell Fate ◽  
Histone Variants ◽  
Epigenetic Memory ◽  
The Core ◽  
Nucleosome Dynamics ◽  
Nucleosome Structure ◽  
Core Histones ◽  
And Function ◽  
The Impact

Nucleosome dynamics and properties are central to all forms of genomic activities. Among the core histones, H3 variants play a pivotal role in modulating nucleosome structure and function. Here, we focus on the impact of H3 variants on various facets of development. The deposition of the replicative H3 variant following DNA replication is essential for the transmission of the epigenomic information encoded in posttranscriptional modifications. Through this process, replicative H3 maintains cell fate while, in contrast, the replacement H3.3 variant opposes cell differentiation during early embryogenesis. In later steps of development, H3.3 and specialized H3 variants are emerging as new, important regulators of terminal cell differentiation, including neurons and gametes. The specific pathways that regulate the dynamics of the deposition of H3.3 are paramount during reprogramming events that drive zygotic activation and the initiation of a new cycle of development.

scholarly journals The Nuclear Actin-related Protein of Saccharomyces cerevisiae, Act3p/Arp4, Interacts with Core Histones

1999 ◽  
Vol 10 (8) ◽  
pp. 2595-2605 ◽  
Author(s):  
Masahiko Harata ◽  
Yukako Oma ◽  
Shigeki Mizuno ◽  
Yi Wei Jiang ◽  
David J. Stillman ◽  
...  
Keyword(s):  
Nuclear Actin ◽  
Histone H2a ◽  
Related Protein ◽  
The Core ◽  
Core Histones ◽  
Episomal Dna ◽  
Two Hybrid ◽  
Far Western Blot ◽  
Correct Expression

Act3p/Arp4, an essential actin-related protein ofSaccharomyces cerevisiae located within the nucleus, is, according to genetic data, involved in transcriptional regulation. In addition to the basal core structure of the actin family members, which is responsible for ATPase activity, Act3p possesses two insertions, insertions I and II, the latter of which is predicted to form a loop-like structure protruding from beyond the surface of the molecule. Because Act3p is a constituent of chromatin but itself does not bind to DNA, we hypothesized that insertion II might be responsible for an Act3p-specific function through its interaction with some other chromatin protein. Far Western blot and two-hybrid analyses revealed the ability of insertion II to bind to each of the core histones, although with somewhat different affinities. Together with our finding of coimmunoprecipitation of Act3p with histone H2A, this suggests the in vivo existence of a protein complex required for correct expression of particular genes. We also show that a conditionalact3 mutation affects chromatin structure of an episomal DNA molecule, indicating that the putative Act3p complex may be involved in the establishment, remodeling, or maintenance of chromatin structures.

Connection between histone H2A variants and chromatin remodeling complexesThis paper is one of a selection of papers published in this Special Issue, entitled CSBMCB’s 51st Annual Meeting – Epigenetics and Chromatin Dynamics, and has undergone the Journal’s usual peer review process.

2009 ◽  
Vol 87 (1) ◽  
pp. 35-50 ◽  
Author(s):  
Mohammed Altaf ◽  
Andréanne Auger ◽  
Marcela Covic ◽  
Jacques Côté
Keyword(s):  
Chromatin Remodeling ◽  
Chromatin Structure ◽  
Cellular Response ◽  
Peer Review Process ◽  
Histone Variants ◽  
Histone H2a ◽  
Chromatin Dynamics ◽  
Recent Developments ◽  
Chromatin Remodeling Complexes ◽  
And Function

The organization of the eukaryotic genome into chromatin makes it inaccessible to the factors required for gene transcription and DNA replication, recombination, and repair. In addition to histone-modifying enzymes and ATP-dependent chromatin remodeling complexes, which play key roles in regulating many nuclear processes by altering the chromatin structure, cells have developed a mechanism of modulating chromatin structure by incorporating histone variants. These variants are incorporated into specific regions of the genome throughout the cell cycle. H2A.Z, which is an evolutionarily conserved H2A variant, performs several seemingly unrelated and even contrary functions. Another H2A variant, H2A.X, plays a very important role in the cellular response to DNA damage. This review summarizes the recent developments in our understanding of the role of H2A.Z and H2A.X in the regulation of chromatin structure and function, focusing on their functional links with chromatin modifying and remodeling complexes.

scholarly journals Epigenetic regulation of the histone-to-protamine transition during spermiogenesis

Reproduction ◽  
2016 ◽  
Vol 151 (5) ◽  
pp. R55-R70 ◽  
Author(s):  
Jianqiang Bao ◽  
Mark T Bedford
Keyword(s):  
Transcription Factors ◽  
Germ Cells ◽  
Transition Process ◽  
Histone Variants ◽  
Motile Sperm ◽  
Male Germ Cells ◽  
The Core ◽  
Developmental Program ◽  
Core Histones ◽  
Epigenetic Regulators

Abstract In mammals, male germ cells differentiate from haploid round spermatids to flagella-containing motile sperm in a process called spermiogenesis. This process is distinct from somatic cell differentiation in that the majority of the core histones are replaced sequentially, first by transition proteins and then by protamines, facilitating chromatin hyper-compaction. This histone-to-protamine transition process represents an excellent model for the investigation of how epigenetic regulators interact with each other to remodel chromatin architecture. Although early work in the field highlighted the critical roles of testis-specific transcription factors in controlling the haploid-specific developmental program, recent studies underscore the essential functions of epigenetic players involved in the dramatic genome remodeling that takes place during wholesale histone replacement. In this review, we discuss recent advances in our understanding of how epigenetic players, such as histone variants and histone writers/readers/erasers, rewire the haploid spermatid genome to facilitate histone substitution by protamines in mammals.

GATA-1, NF-E2 and EKLF/SP1 Binding Elements Cooperate To Specify Patterns of Histone Hyper-Acetylation at β-Globin LCR HS Core Elements.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1208-1208
Author(s):  
Catherine J. Ackley ◽  
Christopher H. Lowrey
Keyword(s):  
Histone Acetylation ◽  
Internal Control ◽  
Chromatin Structure ◽  
Binding Sites ◽  
Globin Genes ◽  
Factor Binding ◽  
The Core ◽  
Active Elements ◽  
Core Histones ◽  
Core Elements

Abstract The active elements of the β-globin LCR are necessary for high-level expression of the linked globin genes. These active elements are contained within regions of unique, erythroid-specific chromatin structure characterized by the formation of positioned nucleosomal arrays, areas of approximately 150–200 bp which are highly accessible for protein-DNA interactions (DNase I HSs) and hyperacetylation of histones H3 and H4. At a DNA level, each of the LCR HS cores contain NF-E2, EKLF/Sp1 and tandem, inverted GATA binding elements. Our lab has shown that all of these transcription factor-binding sites are necessary for HS formation. We have previously proposed a model of HS formation in which Sp1 and/or EKLF first bind to the core regions and alter local chromatin structure allowing GATA-1 and NF-E2 to bind and stabilize the HS core structure. Additional factors could then bind to the core and flanking regions. An important aspect of HS core formation that our experiments have not previously addressed is the mechanism of histone acetylation. Based on our previous findings and the fact that GATA-1 and NF-E2 can both interact with histone acetyltransferases (HATs), we hypothesized that histone acetylation at the HS requires the binding of EKLF/Sp1 followed by GATA-1 and/or NF-E2 and therefor should be a late event in HS formation. To test this hypothesis, we have generated a series of 11 artificial HS core elements based on the structure of human HS4. These plasmid-based constructs contain different combinations of the six binding sites in their normal arrangement and spacing: (EKLF/Sp1)-(NF-E2)-(EKLF/SP1)-(GATA-1 x 2)-(EKLF/Sp1). These constructs were stably transfected into MEL cells and assayed for their ability to mediate histone H3 and H4 acetylation as determined by the ChIP assay. The endogenous murine β-globin LCR HS3 served as a positive internal control for histone acetylation. Previous results from our lab showed that all six factor-binding sites within the HS core are required for HS formation. However, when assayed for histone acetylation, the NF-E2 and the tandem inverted GATA sites are able to independently direct H3 and H4 acetylation to between 10 and 50% of that seen at the native HS site. Combination of the NF-E2 and GATA-1 sites results in 89% of normal H4 acetylation. Full HH4 acetylation (98% of the wild-type HS) is only seen with all six factor binding sites. These results indicate that NF-E2 and GATA-1 direct most of the acetylation of LCR HS core histones but that EKLF binding is also likely to contribute. They also indicate that extensive histone acetylation can occur without HS formation. Finally, in contrast to our model of HS formation, GATA-1 and NF-E2 appear able to direct the acetylation of HS core histones without the presence of binding sites for Sp1 or EKLF.

Further characterization of the posttranslational modifications of core histones in response to heat and arsenite stress in Drosophila

1986 ◽  
Vol 64 (8) ◽  
pp. 750-757 ◽  
Author(s):  
Richard Desrosiers ◽  
Robert M. Tanguay
Keyword(s):  
Heat Shock ◽  
Posttranslational Modifications ◽  
Gel Electrophoresis ◽  
Cultured Cells ◽  
Histone Variants ◽  
Two Dimensional ◽  
Two Dimensional Gel Electrophoresis ◽  
Nonhistone Protein ◽  
The Core ◽  
Core Histones

The effects of a heat shock or arsenite treatment on the methylation and acetylation of core histones have been investigated in Drosophila cultured cells. The decrease in H3 methylation, which is observed during a heat shock, is not a demethylation process, but results from methylation arrest. Two-dimensional gel electrophoresis leaves no ambiguity concerning the identity of H2B as a methylated protein, since H2B and D2, a nuclear nonhistone protein, which comigrate on one-dimensional gels, are well separated on these gels. Two-dimensional gel electrophoresis in the presence of Triton X-100 resolves each of the core histones into multiple forms resulting from posttranslational modifications. There are apparently, however, no histone variants in cultured Drosophila cells. At 23 °C, the various forms of the core histones resolved on two-dimensional gels are methylated. Under heat-shock or arsenite treatment, the methylation of all forms of H3 is decreased, while that of the various forms of H2B increases. These stress conditions also induce a generalized diminution in the acetylation of all forms of core histones. In the course of a heat shock, the synthesis of H2B is increased and this newly synthesized histone remains unacetylated during the shock. These changes in the patterns of core histone methylation and acetylation may be correlated with the reorganization of gene activity brought about by the heat shock.

scholarly journals Assembly and Disassembly of Nucleosome Core Particles Containing Histone Variants by Human Nucleosome Assembly Protein I

2005 ◽  
Vol 25 (23) ◽  
pp. 10639-10651 ◽  
Author(s):  
Mitsuru Okuwaki ◽  
Kohsuke Kato ◽  
Hideto Shimahara ◽  
Shin-ichi Tate ◽  
Kyosuke Nagata
Keyword(s):  
Chromatin Structure ◽  
Histone Variants ◽  
Biochemical Properties ◽  
Histone H2a ◽  
Nucleosome Assembly ◽  
Active Chromatin ◽  
Nucleosome Core ◽  
Nucleosome Assembly Protein ◽  
Nucleosome Core Particles ◽  
Core Particles

ABSTRACT Histone variants play important roles in the maintenance and regulation of the chromatin structure. In order to characterize the biochemical properties of the chromatin structure containing histone variants, we investigated the dynamic status of nucleosome core particles (NCPs) that were assembled with recombinant histones. We found that in the presence of nucleosome assembly protein I (NAP-I), a histone chaperone, H2A-Barr body deficient (H2A.Bbd) confers the most flexible nucleosome structure among the mammalian histone H2A variants known thus far. NAP-I mediated the efficient assembly and disassembly of the H2A.Bbd-H2B dimers from NCPs. This reaction was accomplished more efficiently when the NCPs contained H3.3, a histone H3 variant known to be localized in the active chromatin, than when the NCPs contained the canonical H3. These observations indicate that the histone variants H2A.Bbd and H3.3 are involved in the formation and maintenance of the active chromatin structure. We also observed that acidic histone binding proteins, TAF-I/SET and B23.1, demonstrated dimer assembly and disassembly activity, but the efficiency of their activity was considerably lower than that of NAP-I. Thus, both the acidic nature of NAP-I and its other functional structure(s) may be essential to mediate the assembly and disassembly of the dimers in NCPs.

H2AX: tailoring histone H2A for chromatin-dependent genomic integrity

2005 ◽  
Vol 83 (4) ◽  
pp. 505-515 ◽  
Author(s):  
Andra Li ◽  
José M Eirín-López ◽  
Juan Ausió
Keyword(s):  
Chromatin Structure ◽  
Histone Variants ◽  
Environmental Damage ◽  
Structural Level ◽  
Histone H2a ◽  
Dna Breaks ◽  
Histone H2ax ◽  
Double Stranded Dna ◽  
Chromatin Remodeling Complexes ◽  
And Function

During the last decade, chromatin research has been focusing on the role of histone variability as a modulator of chromatin structure and function. Histone variability can be the result of either post-translational modifications or intrinsic variation at the primary structure level: histone variants. In this review, we center our attention on one of the most extensively characterized of such histone variants in recent years, histone H2AX. The molecular phylogeny of this variant seems to have run in parallel with that of the major canonical somatic H2A1 in eukaryotes. Functionally, H2AX appears to be mainly associated with maintaining the genome integrity by participating in the repair of the double-stranded DNA breaks exogenously introduced by environmental damage (ionizing radiation, chemicals) or in the process of homologous recombination during meiosis. At the structural level, these processes involve the phosphorylation of serine at the SQE motif, which is present at the very end of the C-terminal domain of H2AX, and possibly other PTMs, some of which have recently started to be defined. We discuss a model to account for how these H2AX PTMs in conjunction with chromatin remodeling complexes (such as INO80 and SWRI) can modify chromatin structure (remodeling) to support the DNA unraveling ultimately required for DNA repair.Key words: H2AX, DNA repair, double-stranded DNA breaks, phosphorylation.

scholarly journals Biparental contributions of the H2A.B histone variant control embryonic development in mice

PLoS Biology ◽  
2020 ◽  
Vol 18 (12) ◽  
pp. e3001001
Author(s):  
Antoine Molaro ◽  
Anna J. Wood ◽  
Derek Janssens ◽  
Selina M. Kindelay ◽  
Michael T. Eickbush ◽  
...  
Keyword(s):  
Germ Cells ◽  
Chromatin Structure ◽  
Histone Variants ◽  
Histone H2a ◽  
Biological Functions ◽  
Mammalian Development ◽  
Parental Effect ◽  
Males And Females ◽  
Embryonic Viability ◽  
Effect Gene

Histone variants expand chromatin functions in eukaryote genomes. H2A.B genes are testis-expressed short histone H2A variants that arose in placental mammals. Their biological functions remain largely unknown. To investigate their function, we generated a knockout (KO) model that disrupts all 3 H2A.B genes in mice. We show that H2A.B KO males have globally altered chromatin structure in postmeiotic germ cells. Yet, they do not show impaired spermatogenesis or testis function. Instead, we find that H2A.B plays a crucial role postfertilization. Crosses between H2A.B KO males and females yield embryos with lower viability and reduced size. Using a series of genetic crosses that separate parental and zygotic contributions, we show that the H2A.B status of both the father and mother, but not of the zygote, affects embryonic viability and growth during gestation. We conclude that H2A.B is a novel parental-effect gene, establishing a role for short H2A histone variants in mammalian development. We posit that parental antagonism over embryonic growth drove the origin and ongoing diversification of short histone H2A variants in placental mammals.

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