scholarly journals Crosstalks between NOD1 and Histone H2A Contribute to Host Defense against Streptococcus agalactiae Infection in Zebrafish

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 861
Author(s):  
Xiaoman Wu ◽  
Fan Xiong ◽  
Hong Fang ◽  
Jie Zhang ◽  
Mingxian Chang
Keyword(s):  
Host Defense ◽  
Streptococcus Agalactiae ◽  
Metabolic Pathways ◽  
Synergetic Effect ◽  
Histone Variants ◽  
Larval Survival ◽  
Histone H2a ◽  
Adult Zebrafish ◽  
Correlation Studies ◽  
Functional Correlation

Correlation studies about NOD1 and histones have not been reported. In the present study, we report the functional correlation between NOD1 and the histone H2A variant in response to Streptococcus agalactiae infection. In zebrafish, NOD1 deficiency significantly promoted S. agalactiae proliferation and decreased larval survival. Transcriptome analysis revealed that the significantly enriched pathways in NOD1−/− adult zebrafish were mainly involved in immune and metabolism. Among 719 immunity-associated DEGs at 48 hpi, 74 DEGs regulated by NOD1 deficiency were histone variants. Weighted gene co-expression network analysis identified that H2A, H2B, and H3 had significant associations with NOD1 deficiency. Above all, S. agalactiae infection could induce the expression of intracellular histone H2A, as well as NOD1 colocalized with histone H2A, both in the cytoplasm and cell nucleus in the case of S. agalactiae infection. The overexpression of H2A variants such as zfH2A-6 protected against S. agalactiae infection and could improve cell survival in NOD1-deficient cells. Furthermore, NOD1 could interact with zfH2A-6 and cooperate with zfH2A-6 to inhibit the proliferation of S. agalactiae. NOD1 also showed a synergetic effect in inducing the expression of many antibacterial genes, especially antibacterial pattern recognition receptors PGRP2, PGRP5, and PGRP6. Collectively, these results firstly highlight the roles of NOD1 deficiency in the regulation of immune-related and metabolic pathways, and the correlation between zebrafish NOD1 and histone H2A variant in the defense against S. agalactiae infection.

scholarly journals Phosphorylation within Intrinsic Disordered Region Discriminates Histone Variant macroH2A1 Splicing Isoforms—macroH2A1.1 and macroH2A1.2

Biology ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 659
Author(s):  
Sebastiano Giallongo ◽  
Oriana Lo Re ◽  
Gabriela Lochmanová ◽  
Luca Parca ◽  
Francesco Petrizzelli ◽  
...  
Keyword(s):  
Fluorescent Protein ◽  
Regulatory Element ◽  
Histone Variants ◽  
Histone H2a ◽  
Human Hepatoma Cells ◽  
Nucleosome Core ◽  
Intrinsically Disordered ◽  
Splicing Isoforms ◽  
The Impact

Background: Gene expression in eukaryotic cells can be governed by histone variants, which replace replication-coupled histones, conferring unique chromatin properties. MacroH2A1 is a histone H2A variant containing a domain highly similar to H2A and a large non-histone (macro) domain. MacroH2A1, in turn, is present in two alternatively exon-spliced isoforms: macroH2A1.1 and macroH2A1.2, which regulate cell plasticity and proliferation in a remarkably distinct manner. The N-terminal and the C-terminal tails of H2A histones stem from the nucleosome core structure and can be target sites for several post-translational modifications (PTMs). MacroH2A1.1 and macroH2A1.2 isoforms differ only in a few amino acids and their ability to bind NAD-derived metabolites, a property allegedly conferring their different functions in vivo. Some of the modifications on the macroH2A1 variant have been identified, such as phosphorylation (T129, S138) and methylation (K18, K123, K239). However, no study to our knowledge has analyzed extensively, and in parallel, the PTM pattern of macroH2A1.1 and macroH2A1.2 in the same experimental setting, which could facilitate the understanding of their distinct biological functions in health and disease. Methods: We used a mass spectrometry-based approach to identify the sites for phosphorylation, acetylation, and methylation in green fluorescent protein (GFP)-tagged macroH2A1.1 and macroH2A1.2 expressed in human hepatoma cells. The impact of selected PTMs on macroH2A1.1 and macroH2A1.2 structure and function are demonstrated using computational analyses. Results: We identified K7 as a new acetylation site in both macroH2A1 isoforms. Quantitative comparison of histone marks between the two isoforms revealed significant differences in the levels of phosphorylated T129 and S170. Our computational analysis provided evidence that the phosphorylation status in the intrinsically disordered linker region in macroH2A1 isoforms might represent a key regulatory element contributing to their distinct biological responses. Conclusions: Taken together, our results report different PTMs on the two macroH2A1 splicing isoforms as responsible for their distinct features and distribution in the cell.

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.

Proteome analysis of protein partners to nucleosomes containing canonical H2A or the variant histones H2A.Z or H2A.X

2012 ◽  
Vol 393 (1-2) ◽  
pp. 47-61 ◽  
Author(s):  
Satoru Fujimoto ◽  
Corrine Seebart ◽  
Tiziana Guastafierro ◽  
Jessica Prenni ◽  
Paola Caiafa ◽  
...  
Keyword(s):  
Regulation Of Gene Expression ◽  
Proteome Analysis ◽  
Strand Break ◽  
Histone Variants ◽  
Histone H2a ◽  
Systematic Analysis ◽  
Cellular Processes ◽  
Nucleosome Structure ◽  
Protein Partners ◽  
Dna Double Strand Break

Abstract Although the existence of histone variants has been known for quite some time, only recently are we grasping the breadth and diversity of the cellular processes in which they are involved. Of particular interest are the two variants of histone H2A, H2A.Z and H2A.X because of their roles in regulation of gene expression and in DNA double-strand break repair, respectively. We hypothesize that nucleosomes containing these variants may perform their distinct functions by interacting with different sets of proteins. Here, we present our proteome analysis aimed at identifying protein partners that interact with nucleosomes containing H2A.Z, H2A.X or their canonical H2A counterpart. Our development of a nucleosome-pull down assay and analysis of the recovered nucleosome-interacting proteins by mass spectrometry allowed us to directly compare nuclear partners of these variant-containing nucleosomes to those containing canonical H2A. To our knowledge, our data represent the first systematic analysis of the H2A.Z and H2A.X interactome in the context of nucleosome structure.

Adult zebrafish model of bacterial meningitis in Streptococcus agalactiae infection

2012 ◽  
Vol 38 (3) ◽  
pp. 447-455 ◽  
Author(s):  
Hayley Patterson ◽  
Anni Saralahti ◽  
Mataleena Parikka ◽  
Shaynoor Dramsi ◽  
Patrick Trieu-Cuot ◽  
...  
Keyword(s):  
Bacterial Meningitis ◽  
Streptococcus Agalactiae ◽  
Adult Zebrafish ◽  
Zebrafish Model

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

2017 ◽  
Author(s):  
Antoine Molaro ◽  
Janet M. Young ◽  
Harmit S. Malik
Keyword(s):  
Genome Stability ◽  
Histone Variants ◽  
Histone Variant ◽  
Histone H2a ◽  
Genetic Conflict ◽  
Post Translational Modifications ◽  
Evolutionary Origins ◽  
Male Germline ◽  
Early Diversification ◽  
Canonical Histone

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.

scholarly journals A fine-scale multi-step approach to understand fish recruitment variability

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Pablo Brosset ◽  
Andrew Douglas Smith ◽  
Stéphane Plourde ◽  
Martin Castonguay ◽  
Caroline Lehoux ◽  
...  
Keyword(s):  
Egg Production ◽  
Adult Population ◽  
Synergetic Effect ◽  
Fish Population ◽  
Larval Survival ◽  
Population Characteristics ◽  
Environmental Drivers ◽  
Fine Scale ◽  
Atlantic Mackerel ◽  
Spatio Temporal

Abstract Recruitment is one of the dominant processes regulating fish population productivity. It is, however, notoriously difficult to predict, as it is the result of a complex multi-step process. Various fine-scale drivers might act on the pathway from adult population characteristics to spawning behaviour and egg production, and then to recruitment. Here, we provide a holistic analysis of the Northwest Atlantic mackerel recruitment process from 1982 to 2017 and exemplify why broad-scale recruitment–environment relationships could become unstable over time. Various demographic and environmental drivers had a synergetic effect on recruitment, but larval survival through a spatio-temporal match with prey was shown to be the key process. Recruitment was also mediated by maternal effects and a parent–offspring fitness trade-off due to the different feeding regimes of adults and larvae. A mismatch curtails the effects of high larval prey densities, so that despite the abundance of food in recent years, recruitment was relatively low and the pre-existing relationship with overall prey abundance broke down. Our results reaffirm major recruitment hypotheses and demonstrate the importance of fine-scale processes along the recruitment pathway, helping to improve recruitment predictions and potentially fisheries management.

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.

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 Toxicometabolomics of lindane in adult zebrafish (Danio rerio) using GC-MS/MS and LC-Orbitrap-MS/MS

2021 ◽  
Vol 64 (1) ◽  
Author(s):  
Xiu Yuan ◽  
Junghak Lee ◽  
Eunyoung Park ◽  
Hwa-Kyung Lee ◽  
Jeong-Han Kim
Keyword(s):  
Metabolic Pathways ◽  
Pentose Phosphate ◽  
Adult Zebrafish ◽  
Targeted Metabolomics ◽  
High Concentration ◽  
High Exposure ◽  
Toxicological Effects ◽  
Phenylalanine Metabolism ◽  
Low Exposure ◽  
Orbitrap Ms

AbstractLindane is a broad-spectrum persistent organochlorine pesticide that has been used to control pests for many years. In this study, its toxic mechanisms in adult zebrafish were investigated using targeted metabolomics with GC-MS/MS and non-targeted metabolomics with LC-Orbitrap-MS/MS. Zebrafish was exposed to lindane in water for 48 h in three groups: control, low exposure (1/10 LC50) and high exposure (LC50). In the zebrafish exposed to low concentration of lindane, 2.24–3.98 mg/kg of lindane were determined, while 35.67–56.46 mg/kg were observed in the zebrafish exposed to high concentration. A total of 118 metabolites were identified from 394 metabolites on GC-MS/MS and 45 metabolites were selected as biomarkers. A total of 62 metabolites were identified on LC-Orbitrap-MS/MS and 7 metabolites were selected as biomarkers. Three groups were well separated on partial least squares-discriminant analysis (PLS-DA), and a total of 52 metabolites in both the targeted and non-targeted metabolites were selected as biomarkers through VIP and ANOVA tests to construct a heatmap. Five metabolic pathways such as the pentose phosphate pathway (PPP), histidine metabolism, phenylalanine metabolism, alanine/aspartate/glutamate metabolism, and phenylalanine/tyrosine/tryptophan biosynthesis, were observed to show toxicologically significant alterations. Oxidative stress was also confirmed through MDA and ROS assays. Such perturbations of the metabolic pathways of zebrafish caused by the exposure to lindane resulted in significant toxicological effects.

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