ChIP on chip "Epigenomic modifications predict active promoters and gene structure in Toxoplasma gondii"
Ontology highlight
ABSTRACT:
ORGANISM(S): Toxoplasma gondii Toxoplasma gondii RH
PROVIDER: GSE5992 | GEO | 2007/05/22
SECONDARY ACCESSION(S): PRJNA104431
REPOSITORIES: GEO
Similar Datasets
Project description:Mechanisms of gene regulation are poorly understood in Apicomplexa, a phylum that encompasses deadly human pathogens like Plasmodium and Toxoplasma. Initial studies suggest that epigenetic phenomena, including histone modifications and chromatin remodeling, have a profound effect upon gene expression and expression of virulence traits. Using the model organism Toxoplasma gondii, we characterized the epigenetic organization and transcription patterns of a contiguous 1% of the T. gondii genome using custom oligonucleotide microarrays. We show that methylation and acetylation of histones H3 and H4 are landmarks of active promoters in T. gondii that allow us to deduce the position and directionality of gene promoters with >95% accuracy. These histone methylation and acetylation "activation" marks are strongly associated with gene expression. We also demonstrate that the pattern of histone H3 arginine methylation distinguishes certain promoters, illustrating the complexity of the histone modification machinery in Toxoplasma. By integrating epigenetic data, gene prediction analysis, and gene expression data from the tachyzoite stage, we illustrate feasibility of creating an epigenomic map of T. gondii tachyzoite gene expression. Further, we illustrate the utility of the epigenomic map to empirically and biologically annotate the genome and show that this approach enables identification of previously unknown genes. Thus, our epigenomics approach provides novel insights into regulation of gene expression in the Apicomplexa. In addition, with its compact genome, genetic tractability, and discrete life cycle stages, T. gondii provides an important new model to study the evolutionarily conserved components of the histone code.
| S-EPMC1891328 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2007-05-21 | GSE7262 | GEO
Project description:total RNA was extracted after 24 hours of development of the RH strain in HFF cells. Keywords: gene expression
2007-05-22 | GSE5989 | GEO
Project description:Gene expression "Epigenomic modifications predict active promoters and gene structure in Toxoplasma gondii"
| PRJNA104429 | ENA
Project description:ChIP-seq to identify Venus-IWS1 on Toxoplasma GT-1 genome
| PRJDB14820 | ENA
Project description:ChIP on chip "Epigenomic modifications predict active promoters and gene structure in Toxoplasma gondii"
| PRJNA104431 | ENA
Project description:Chromatin is composed of DNA wrapped around nucleosomes, complexes consisting of highly basic proteins called histones. Histone variants are non-canonical variants of histones that have specific functions. The Apicomplexan parasite Toxoplasma gondii possesses conserved histone variants CenH3, H3.3, H2A.Z, H2A.X, as well as the parasite-specific H2B variant, H2BV (or H2B.Z). We surveyed the genome-wide distribution of T. gondii histone variants by chromatin immunoprecipitation coupled with microarray (ChIP-chip) and next generation sequencing (ChIP-seq). Histone variants have specific localisations in chromosomes and in relation to genomic features. Histones H2BV and H2AZ localise to promoter regions with the transcriptional activation mark H3K4me3. Sites where H2BV, H2AZ and H3K4me3 colocalise are enriched in motifs recognised by AP2 transcription factors, particularly in the nucleosome-free region just upstream of the transcription start site. In contrast, histone variants H3.3 and H2AX are largely absent from promoters but enriched in gene bodies. Consistent with previous biochemical work, the majority of H2AX and H2AZ loci do not overlap, suggesting that they are present in different nucleosomes. In addition, the T. gondii homologue of the centromeric histone CenH3 demarcates centromeric chromatin and appears to be part of a unique centromeric histone complex including H3.3 that localises to centromeric chromatin as detected in proteomic analysis of co-immunoprecipitated CenH3 complexes. Together, these data suggest that the position of variant histones demarcates specific functional regions of chromatin and that exchange of histone variants is an important transcriptional regulatory mechanism in T. gondii.
2018-03-01 | GSE104347 | GEO
Project description:UNLABELLED:Epigenetic gene regulation has emerged as a major mechanism for gene regulation in all eukaryotes. Histones are small, basic proteins that constitute the major protein component of chromatin, and posttranslational modifications (PTM) of histones are essential for epigenetic gene regulation. The different combinations of histone PTM form the histone code for an organism, marking functional units of chromatin that recruit macromolecular complexes that govern chromatin structure and regulate gene expression. To characterize the repertoire of Toxoplasma gondii histone PTM, we enriched histones using standard acid extraction protocols and analyzed them with several complementary middle-down and bottom-up proteomic approaches with the high-resolution Orbitrap mass spectrometer using collision-induced dissociation (CID), higher-energy collisional dissociation (HCD), and/or electron transfer dissociation (ETD) fragmentation. We identified 249 peptides with unique combinations of PTM that comprise the T. gondii histone code. T. gondii histones share a high degree of sequence conservation with human histones, and many modifications are conserved between these species. In addition, T. gondii histones have unique modifications not previously identified in other species. Finally, T. gondii histones are modified by succinylation, propionylation, and formylation, recently described histone PTM that have not previously been identified in parasitic protozoa. The characterization of the T. gondii histone code will facilitate in-depth analysis of how epigenetic regulation affects gene expression in pathogenic apicomplexan parasites and identify a new model system for elucidating the biological functions of novel histone PTM. IMPORTANCE:Toxoplasma gondii is among the most common parasitic infections in humans. The transition between the different stages of the T. gondii life cycle are essential for parasite virulence and survival. These differentiation events are accompanied by significant changes in gene expression, and the control mechanisms for these transitions have not been elucidated. Important mechanisms that are involved in the control of gene expression are the epigenetic modifications that have been identified in several eukaryotes. T. gondii has a full complement of histone-modifying enzymes, histones, and variants. In this paper, we identify over a hundred PTM and a full repertoire of PTM combinations for T. gondii histones, providing the first large-scale characterization of the T. gondii histone code and an essential initial step for understanding how epigenetic modifications affect gene expression and other processes in this organism.
| S-EPMC3870261 | biostudies-literature
Project description:The apicomplexan parasite Toxoplasma gondii must invade host cells to continue its lifecycle. It invades different cell types using an actomyosin motor that is connected to extracellular adhesins via the bridging protein fructose-1,6-bisphosphate aldolase. During invasion, aldolase serves in the role of a structural bridging protein, as opposed to its normal enzymatic role in the glycolysis pathway. Crystal structures of the homologous Plasmodium falciparum fructose-1,6-bisphosphate aldolase have been described previously. Here, T. gondii fructose-1,6-bisphosphate aldolase has been crystallized in space group P22121, with the biologically relevant tetramer in the asymmetric unit, and the structure has been determined via molecular replacement to a resolution of 2.0?Å. An analysis of the quality of the model and of the differences between the four chains in the asymmetric unit and a comparison between the T. gondii and P. falciparum aldolase structures is presented.
| S-EPMC4157416 | biostudies-literature
Project description:Toxoplasma gondii is a protozoan parasite that infects nearly all mammal and bird species worldwide. Usually asymptomatic, toxoplasmosis can be severe and even fatal to many hosts, including people. Elucidating the contribution of genetic variation among parasites to patterns of disease transmission and manifestations has been the goal of many studies. Focusing on the geographic component of this variation, we show that most genotypes are locale-specific, but some are found across continents and are closely related to each other, indicating a recent radiation of a pandemic genotype. Furthermore, we show that the geographic structure of T. gondii is extraordinary in having one population that is found in all continents except South America, whereas other populations are generally confined to South America, and yet another population is found worldwide. Our evidence suggests that South American and Eurasian populations have evolved separately until recently, when ships populated by rats, mice, and cats provided T. gondii with unprecedented migration opportunities, probably during the transatlantic slave trade. Our results explain several enigmatic features of the population structure of T. gondii and demonstrate how pervasive, prompt, and elusive the impact of human globalization is on nature.
| S-EPMC1544101 | biostudies-literature