Histones and histone modifications in protozoan parasites

Sullivan, William J.; Naguleswaran, Arunasalam; Angel, Sérgio O.

doi:10.1111/j.1462-5822.2006.00818.x

Cited by 74 publications

(63 citation statements)

References 75 publications

(113 reference statements)

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“…5 A large number of SSRs are found in subtelomeric regions, where most of the genes encoding the various surface antigens in T. cruzi are located. Hence, several sequences from the cloned ChIP material enriched in acetylated H3 corresponded to surface antigen genes flanking the HH SSRs.…”

Section: Discussionmentioning

confidence: 99%

“…The rarity of canonical transcription factors and regulatory DNA sequences points toward gene expression control through modulations of chromatin structures instead of the traditional modes of transcriptional control. Evidently, epigenetic regulation mediated through chromatin modifications would influence important processes such as antigen variation, virulence, and differentiation in trypanosomes and other protozoan parasites (5).…”

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confidence: 99%

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Histone Acetylation and Methylation at Sites Initiating Divergent Polycistronic Transcription in Trypanosoma cruzi

Respuela

Ferella

Rada-Iglesias

et al. 2008

Journal of Biological Chemistry

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Trypanosomes are ancient eukaryotic parasites in which the protein-coding genes, organized in large polycistronic clusters on both strands, are transcribed from as yet unidentified promoters. In an effort to reveal transcriptional initiation sites, we examined the Trypanosoma cruzi genome for histone modification patterns shown to be linked to active genes in various organisms. Here, we show that acetylated and methylated histones were found to be enriched at strand switch regions of divergent gene arrays, not at convergent clusters or intra-and intergenic regions within clusters. The modified region showed a bimodular profile with two peaks centered over the 5-regions of the gene pair flanking the strand switch region. This pattern, which demarcates polycistronic transcription units originating from bidirectional initiation sites, is likely to be common in kinetoplastid parasites as well as in other organisms with polycistronic transcription. In contrast, no acetylation was found at promoters of the highly expressed rRNA and spliced leader genes or satellite DNA or at tested retrotransposonal elements. These results reveal, for the first time, the presence of specific epigenetic marks in T. cruzi with potential implications for transcriptional regulation; they indicate that both histone modifications and bidirectional transcription are evolutionarily conserved.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Histone Acetylation and Methylation at Sites Initiating Divergent Polycistronic Transcription in Trypanosoma cruzi

Respuela

Ferella

Rada-Iglesias

et al. 2008

Journal of Biological Chemistry

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“…Computational analysis of the T. gondii genome reveals three putative histone H3 genes. Genes TGME49_061240 and TGME49_018260 (toxodb.org version 6.2) appear to encode the canonical H3 and H3.3 variants (17,18). TGME49_025410 encodes an H3 protein with a unique 99-amino acid insertion at the N terminus (see multiple sequence…”

Section: Resultsmentioning

confidence: 99%

Toxoplasma gondii sequesters centromeres to a specific nuclear region throughout the cell cycle

Brooks

Francia

Gissot

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

161

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Members of the eukaryotic phylum Apicomplexa are the cause of important human diseases including malaria, toxoplasmosis, and cryptosporidiosis. These obligate intracellular parasites produce new invasive stages through a complex budding process. The budding cycle is remarkably flexible and can produce varied numbers of progeny to adapt to different host-cell niches. How this complex process is coordinated remains poorly understood. Using Toxoplasma gondii as a genetic model, we show that a key element to this coordination is the centrocone, a unique elaboration of the nuclear envelope that houses the mitotic spindle. Exploiting transgenic parasite lines expressing epitope-tagged centromeric H3 variant CenH3, we identify the centromeres of T. gondii chromosomes by hybridization of chromatin immunoprecipitations to genome-wide microarrays (ChIP-chip). We demonstrate that centromere attachment to the centrocone persists throughout the parasite cell cycle and that centromeres localize to a single apical region within the nucleus. Centromere sequestration provides a mechanism for the organization of the Toxoplasma nucleus and the maintenance of genome integrity.histone | mitosis

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“…Moreover, inhibition of PfGCN5 activity in vivo by a polyphenolic compound curcumin leads to hypoacetylation of histones, which may partially contribute to the toxicity of curcumin (10). This further testifies to the potential of enzymes regulating covalent modifications of histones as targets for novel chemotherapy of parasitic diseases (55).…”

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confidence: 89%

PfGCN5-Mediated Histone H3 Acetylation Plays a Key Role in Gene Expression in Plasmodium falciparum

et al. 2007

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Histone acetylation, regulated by the opposing actions of histone acetyltransferases (HATs) and deacetylases, is an important epigenetic mechanism in eukaryotic transcription. Although an acetyltransferase (PfGCN5) has been shown to preferentially acetylate histone H3 at K9 and K14 in Plasmodium falciparum, the scale of histone acetylation in the parasite genome and its role in transcriptional activation are essentially unknown. Using chromatin immunoprecipitation (ChIP) and DNA microarray, we mapped the global distribution of PfGCN5, histone H3K9 acetylation (H3K9ac) and trimethylation (H3K9m3) in the P. falciparum genome. While the chromosomal distributions of H3K9ac and PfGCN5 were similar, they are radically different from that of H3K9m3. In addition, there was a positive, though weak correlation between relative occupancy of H3K9ac on individual genes and the levels of gene expression, which was inversely proportional to the distance of array elements from the putative translational start codons. In contrast, H3K9m3 was negatively correlated with gene expression. Furthermore, detailed mapping of H3K9ac for selected genes using ChIP and real-time PCR in three erythrocytic stages detected stage-specific peak H3K9ac enrichment at the putative transcriptional initiation sites, corresponding to stage-specific expression of these genes. These data are consistent with H3K9ac and H3K9m3 as epigenetic markers of active and silent genes, respectively. We also showed that treatment with a PfGCN5 inhibitor led to reduced promoter H3K9ac and gene expression. Collectively, these results suggest that PfGCN5 is recruited to the promoter regions of genes to mediate histone acetylation and activate gene expression in P. falciparum.Plasmodium falciparum, the causative agent of malignant tertian malaria, is responsible for more than 300 million cases and 1 to 3 million deaths per year (51). Extensive research efforts have led to the deciphering of its genome, transcriptome, and proteome, which has greatly advanced our understanding of the fundamental biology of the parasite (18, 22). The parasite life cycle encompasses several morphologically distinct stages while alternating between a vertebrate and an invertebrate host. Recent microarray studies revealed that tightly regulated gene expression in the parasite is in the form of a continuous cascade, with the induction of most genes occurring only once, when their products are needed (3, 39). In addition, antigenic variation of the highly polymorphic P. falciparum erythrocyte membrane protein 1 (PfEMP1), a major virulence factor, through monoallelic expression of ϳ60 var genes, is primarily regulated at the transcription level (33). Although how such a global and localized transcription regulation is achieved is poorly understood, recent extensive studies of var gene regulation indicate that epigenetic control plays an important role in these processes (41,45).Compared to transcription in prokaryotes, there is an added layer of complexity in eukaryotes arising from packaging of...

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Histones and histone modifications in protozoan parasites

Cited by 74 publications

References 75 publications

Histone Acetylation and Methylation at Sites Initiating Divergent Polycistronic Transcription in Trypanosoma cruzi

Histone Acetylation and Methylation at Sites Initiating Divergent Polycistronic Transcription in Trypanosoma cruzi

Toxoplasma gondii sequesters centromeres to a specific nuclear region throughout the cell cycle

PfGCN5-Mediated Histone H3 Acetylation Plays a Key Role in Gene Expression in Plasmodium falciparum

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