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 Genes encoding histone proteins are differentially expressed between men and women with diffuse intrinsic pontine glioma and their expression correlates with survival.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Brain Cancer ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Histone Genes ◽  
Histone H4 ◽  
Pontine Glioma ◽  
Histone H2b ◽  
Men And Women ◽  
Genes Encoding ◽  
Pediatric Brain ◽  
Median Survival Rate

Diffuse intrinsic pontine glioma is a pediatric brain cancer and has the lowest median survival rate of all cancers known to man (1). 99% of patients diagnosed with DIPG will expire within 5 years (1). Understanding the transcriptional behavior of tumors in DIPG is critical for the development of novel therapies. In this study, I compared the transcriptomes of tumors from men with DIPG versus that of tumors from women diagnosed with DIPG using a published dataset (2). I found that three histone genes, including HIST1H4C, HIST1H2BD, and HIST1H3D, which encode Histone H4, Histone H2B Type 1D, and Histone H3.1 were among the genes whose expression was most different between the DIPG tumors of men and women. Importantly, the expression level of two of these genes significantly correlated in a linear fashion with the amount of time the patient survived. It has previously been reported that 78% of DIPG tumors contain a mutation in Histone H3.1 (HIST1H3B) (3). This is the first report of differential expression of histone genes in tumors of patients with DIPG.

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 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.

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 Characterization of mussel H2A.Z.2: a new H2A.Z variant preferentially expressed in germinal tissues from Mytilus

2016 ◽  
Vol 94 (5) ◽  
pp. 480-490 ◽  
Author(s):  
Ciro Rivera-Casas ◽  
Rodrigo González-Romero ◽  
Ángel Vizoso-Vazquez ◽  
Manjinder S. Cheema ◽  
M. Esperanza Cerdán ◽  
...  
Keyword(s):  
Expression Patterns ◽  
Sequence Divergence ◽  
Genotoxic Stress ◽  
Histone Variants ◽  
Coding Regions ◽  
Eukaryotic Chromatin ◽  
Core Histones ◽  
And Function ◽  
First Time

Histones are the fundamental constituents of the eukaryotic chromatin, facilitating the physical organization of DNA in chromosomes and participating in the regulation of its metabolism. The H2A family displays the largest number of variants among core histones, including the renowned H2A.X, macroH2A, H2A.B (Bbd), and H2A.Z. This latter variant is especially interesting because of its regulatory role and its differentiation into 2 functionally divergent variants (H2A.Z.1 and H2A.Z.2), further specializing the structure and function of vertebrate chromatin. In the present work we describe, for the first time, the presence of a second H2A.Z variant (H2A.Z.2) in the genome of a non-vertebrate animal, the mussel Mytilus. The molecular and evolutionary characterization of mussel H2A.Z.1 and H2A.Z.2 histones is consistent with their functional specialization, supported on sequence divergence at promoter and coding regions as well as on varying gene expression patterns. More precisely, the expression of H2A.Z.2 transcripts in gonadal tissue and its potential upregulation in response to genotoxic stress might be mirroring the specialization of this variant in DNA repair. Overall, the findings presented in this work complement recent reports describing the widespread presence of other histone variants across eukaryotes, supporting an ancestral origin and conserved role for histone variants in chromatin.

scholarly journals SAS4 and SAS5 Are Locus-Specific Regulators of Silencing in Saccharomyces cerevisiae

Genetics ◽  
1999 ◽  
Vol 153 (1) ◽  
pp. 25-33 ◽  
Author(s):  
Eugenia Y Xu ◽  
Susan Kim ◽  
David H Rivier
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Mating Type ◽  
Chromatin Structure ◽  
Null Alleles ◽  
Negative Regulators ◽  
The Core ◽  
Repressive Chromatin ◽  
Core Histones ◽  
Positive Regulators

Abstract Sir2p, Sir3p, Sir4p, and the core histones form a repressive chromatin structure that silences transcription in the regions near telomeres and at the HML and HMR cryptic mating-type loci in Saccharomyces cerevisiae. Null alleles of SAS4 and SAS5 suppress silencing defects at HMR; therefore, SAS4 and SAS5 are negative regulators of silencing at HMR. This study revealed that SAS4 and SAS5 contribute to silencing at HML and the telomeres, indicating that SAS4 and SAS5 are positive regulators of silencing at these loci. These paradoxical locus-specific phenotypes are shared with null alleles of SAS2 and are unique among phenotypes of mutations in other known regulators of silencing. This work also determined that these SAS genes play roles that are redundant with SIR1 at HML, yet distinct from SIR1 at HMR. Furthermore, these SAS genes are not redundant with each other in silencing HML. Collectively, these data suggest that SAS2, SAS4, and SAS5 constitute a novel class of regulators of silencing and reveal fundamental differences in the regulation of silencing at HML and HMR. We provide evidence for a model that accounts for the observation that these SAS genes are both positive and negative regulators of silencing.

scholarly journals Eukaryotic core histone diversification in light of the histone doublet and DNA topo II genes of Marseilleviridae

2015 ◽  
Author(s):  
Albert J Erives
Keyword(s):  
Topoisomerase Ii ◽  
Domain Architecture ◽  
Histone Variants ◽  
Core Histone ◽  
Histone Fold ◽  
The Core ◽  
Core Histones ◽  
Topo Ii ◽  
Phylogenomic Analyses ◽  
Linear Chromosomes

While eukaryotic and archaean genomes encode the histone fold domain, only eukaryotes encode the core histones H2A, H2B, H3, and H4. Core histones assemble into a hetero-octamer rather than the homo-tetramer of Archaea. Thus it was unexpected that core histone “doublets” were identified in the cytoplasmic replication factories of the Marseilleviridae (MV), one family of Nucleo-Cytoplasmic Large DNA Viruses (NCLDV). Here we analyze the core histone doublet genes from all known Marseilleviridae genomes and show that they encode obligate H2B-H2A and H4-H3 dimers of likely proto-eukaryotic origin. Each MV core histone moiety forms a sister clade to a eukaryotic core histone clade inclusive of canonical core histone paralogs, suggesting that MV core histone moieties diverged prior to eukaryotic neofunctionalizations associated with paired linear chromosomes and variant histone octamer assembly. We also show that all MV genomes encode a eukaryote-like DNA topoisomerase II enzyme that forms a clade that is sister to the eukaryotic clade. As DNA topo II influences histone deposition and chromatin compaction and is the second most abundant nuclear protein after histones, we suggest MV genes underlie a proto-chromatinized replisome that diverged prior to diversification of eukaryotic core histone variants. Thus, combined domain architecture and phylogenomic analyses suggest that a primitive origin for MV chromatin genes is a more parsimonious explanation than horizontal gene transfers + gene fusions + long-branch attraction constrained to each core histone clade. These results imply that core histones were utilized ancestrally in viral DNA compaction, protection from host endonucleases, and/or other unknown processes associated with NCLDV-like progenitors.

scholarly journals A Cluster of Cuticle Protein Genes of Drosophila melanogaster at 65A: Sequence, Structure and Evolution

Genetics ◽  
1997 ◽  
Vol 147 (3) ◽  
pp. 1213-1224
Author(s):  
Jean-Philippe Charles ◽  
Carol Chihara ◽  
Shamim Nejad ◽  
Lynn M Riddiford
Keyword(s):  
Drosophila Melanogaster ◽  
Genomic Dna ◽  
Multiple Copy ◽  
Sequence Structure ◽  
Coding Regions ◽  
The Third ◽  
Genetic Complexity ◽  
Genes Encoding ◽  
Cuticle Protein ◽  
Cuticle Proteins

A 36-kb genomic DNA segment of the Drosophila melanogaster genome containing 12 clustered cuticle genes has been mapped and partially sequenced. The cluster maps at 65A 5-6 on the left arm of the third chromosome, in agreement with the previously determined location of a putative cluster encompassing the genes for the third instar larval cuticle proteins LCP5, LCP6 and LCP8. This cluster is the largest cuticle gene cluster discovered to date and shows a number of surprising features that explain in part the genetic complexity of the LCP5, LCP6 and LCP8 loci. The genes encoding LCP5 and LCP8 are multiple copy genes and the presence of extensive similarity in their coding regions gives the first evidence for gene conversion in cuticle genes. In addition, five genes in the cluster are intronless. Four of these five have arisen by retroposition. The other genes in the cluster have a single intron located at an unusual location for insect cuticle genes.

scholarly journals Essential and nonessential histone H2A variants in Tetrahymena thermophila.

1996 ◽  
Vol 16 (8) ◽  
pp. 4305-4311 ◽  
Author(s):  
X Liu ◽  
B Li ◽  
GorovskyMA
Keyword(s):  
Tetrahymena Thermophila ◽  
Essential Gene ◽  
Histone Variants ◽  
Gene Replacement ◽  
Histone H2a ◽  
Gene Encoding ◽  
Genes Encoding ◽  
Simple Mass ◽  
Essential Function ◽  
High Degree

Although variants have been identified for every class of histone, their functions remain unknown. We have been studying the histone H2A variant hv1 in the ciliated protozoan Tetrahymena thermophila. Sequence analysis indicates that hv1 belongs to the H2A.F/Z type of histone variants. On the basis of the high degree of evolutionary conservation of this class of histones, they are proposed to have one or more distinct and essential functions that cannot be performed by their major H2A counterparts. Considerable evidence supports the hypothesis that the hv1 protein in T. thermophila and hv1-like proteins in other eukaryotes are associated with active chromatin. In T. thermophila, simple mass transformation and gene replacement techniques have recently become available. In this report, we demonstrate that either the HTA1 gene or the HTA2 gene, encoding the major H2As, can be completely replaced by disrupted genes in the polyploid, transcriptionally active macronucleus, indicating that neither of the two genes is essential. However, only some of the HTA3 genes encoding hv1 can be replaced by disrupted genes, indicating that the H2A.F/Z type variants have an essential function that cannot be performed by the major H2A genes. Thus, an essential gene in T. thermophila can be defined by the fact that it can be partially, but not completely, eliminated from the polyploid macronucleus. To our knowledge, this study represents the first use of gene disruption technology to study core histone gene function in any organism other than yeast and the first demonstration of an essential gene in T. thermophila using these methods. When a rescuing plasmid carrying a wild-type HTA3 gene was introduced into the T. thermophila cells, the endogenous chromosomal HTA3 could be completely replaced, defining a gene replacement strategy that can be used to analyze the function of essential genes.

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