Histone H2AZ dimerizes with a novel variant H2B and is enriched at repetitive DNA in<i>Trypanosoma brucei</i>

Lowell, Joanna E.; Kaiser, Franziska; Janzen, Christian J.; Cross, George A.M.

doi:10.1242/jcs.02688

Cited by 70 publications

(100 citation statements)

References 55 publications

(88 reference statements)

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“…In the case of H4K10ac, this most likely reflects the association with pol II transcription start sites (162). Histone variants H2AZ and H2BV are also found at repetitive DNA, such as telomeric repeats and MC DNA (108). These variants do not colocalize with sites of active transcription labeled by BrU incorporation.…”

Section: Trypanosome Chromatinmentioning

confidence: 96%

Cell Biology of the Trypanosome Genome

Daniels

Gull

Wickstead

2010

Microbiol Mol Biol Rev

111

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SUMMARY Trypanosomes are a group of protozoan eukaryotes, many of which are major parasites of humans and livestock. The genomes of trypanosomes and their modes of gene expression differ in several important aspects from those of other eukaryotic model organisms. Protein-coding genes are organized in large directional gene clusters on a genome-wide scale, and their polycistronic transcription is not generally regulated at initiation. Transcripts from these polycistrons are processed by global trans-splicing of pre-mRNA. Furthermore, in African trypanosomes, some protein-coding genes are transcribed by a multifunctional RNA polymerase I from a specialized extranucleolar compartment. The primary DNA sequence of the trypanosome genomes and their cellular organization have usually been treated as separate entities. However, it is becoming increasingly clear that in order to understand how a genome functions in a living cell, we will need to unravel how the one-dimensional genomic sequence and its trans-acting factors are arranged in the three-dimensional space of the eukaryotic nucleus. Understanding this cell biology of the genome will be crucial if we are to elucidate the genetic control mechanisms of parasitism. Here, we integrate the concepts of nuclear architecture, deduced largely from studies of yeast and mammalian nuclei, with recent developments in our knowledge of the trypanosome genome, gene expression, and nuclear organization. We also compare this nuclear organization to those in other systems in order to shed light on the evolution of nuclear architecture in eukaryotes.

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Section: Trypanosome Chromatinmentioning

confidence: 96%

Cell Biology of the Trypanosome Genome

Daniels

Gull

Wickstead

2010

Microbiol Mol Biol Rev

111

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“…The replacement of canonical histones with histone variants can influence the nucleosome stability and chromatin patterns (95,123). Interestingly, in both Trypanosoma brucei and Toxoplasma gondii, H2A.Z interacts with H2Bv and is associated with active genes (31,99). In T. brucei, variant histones are used to mark boundaries of polycistronic transcription units, and nucleosomes containing two variant histones (H2A.Z and H2Bv) are highly enriched at the putative polymerase II transcription start sites (TSS) (137).…”

Section: Malaria Parasite Histones and "Histone Code"mentioning

confidence: 99%

Chromatin-Mediated Epigenetic Regulation in the Malaria Parasite Plasmodium falciparum

2010

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Malaria is a major public health problem in many developing countries, with the malignant tertian parasite Plasmodium falciparum causing the most malaria-associated mortality. Extensive research, especially with the advancement of genomics and transfection tools, has highlighted the fundamental importance of chromatinmediated gene regulation in the developmental program of this early-branching eukaryote. The Plasmodium parasite genomes reveal the existence of both canonical and variant histones that make up the nucleosomes, as well as a full collection of conserved enzymes for chromatin remodeling and histone posttranslational modifications (PTMs). Recent studies have identified a wide array of both conserved and novel histone PTMs in P. falciparum, indicating the presence of a complex and divergent "histone code." Genome-wide analysis has begun to decipher the nucleosome landscape and histone modifications associated with the dynamic organization of chromatin structures during the parasite's life cycle. Focused studies on malaria-specific phenomena such as antigenic variation and red cell invasion pathways shed further light on the involvement of epigenetic mechanisms in these processes. Here we review our current understanding of chromatin-mediated gene regulation in malaria parasites, with specific reference to exemplar studies on antigenic variation and host cell invasion.Malaria continues to be a major cause of mortality and morbidity in tropical countries, bringing a death toll of ϳ1 million each year. Four human parasites (Plasmodium falciparum, P. vivax, P. malariae, and P. ovale) and a monkey parasite (P. knowlesi) have been found to infect humans naturally. P. falciparum causes the malignant form of malaria and is responsible for most malaria-associated human deaths. Intensified research in the past decade has greatly improved our understanding of the parasites and the disease they cause, especially with the sequencing of multiple parasite genomes. A striking finding from global microarray analyses of parasite gene expression is the tightly regulated transcription program during the parasite's life cycle, with genes expressed in a "just-in-time" manner (12, 93). Bioinformatic analysis has recognized a general conservation of the basal transcription machinery (15), but the scarcity of recognizable specific transcription factors in the parasite genome has led to speculation about the existence of a divergent transcription mechanism used by the malaria parasites (2, 25). However, this speculation may be inaccurate, as recent studies revealed the presence of the AP2 family of transcription factors (4, 35), which have undergone lineagespecific expansion in apicomplexan parasites (75). Nevertheless, the full complement of chromatin-modifying proteins encoded in apicomplexan parasite genomes underlines the significance of epigenetic mechanisms in transcription regulation (2,66,75,140). While epigenetic mechanisms are being intensively studied in model eukaryotes, only recently have they been explored in the m...

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“…They also contain variants of H2, H3, and H4, namely H2Az, H2BV, and H3V. Like most trypanosome genes that are orthologous to those defined in characterized systems, the trypanosome histones also diverge substantially from those in well-studied organisms (8,23,28,36). Small group modifications, mainly acetylation and methylation that occur on lysines and arginines, are present and reflect the importance of the histone code throughout evolution.…”

Section: Epigenetic Control Of Transcriptionmentioning

confidence: 99%

RNA Polymerase Transcription Machinery in Trypanosomes

2008

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Transcription is a fundamental biological process employed by all living organisms to decode their genetic information. The information stored in genomic DNA is copied into RNA molecules by polymerization of ribonucleotide building blocks, which ultimately gives rise to different classes of transcripts. mRNAs encode polypeptides, rRNAs drive the macromolecular protein-synthesis machinery, and tRNAs act as adaptor molecules to assemble amino acids into proteins. Synthesis of specific transcripts is influenced by environmental and internal cell signals, which in turn are pivotal for the control of cellular regulatory networks.Trypanosomes are unicellular parasitic protozoa, members of the order Kinetoplastidae, which diverged early during evolution. They cause a wide range of debilitating diseases in humans and domestic animals. Trypanosoma brucei, known as the African trypanosome, is transmitted by tsetse flies in subSaharan Africa (15). Infection fulminates into African sleeping sickness in humans and nagana in animals (3). T. brucei is a digenetic parasite that cycles as a procyclic form in the digestive tract of the tsetse vector and as an extracellular bloodstream form in its mammalian host. During its complex life cycle, the parasite passes through five successive morphologically distinct forms (39). Parasites change from the procyclic form, which is characterized by a procyclic-specific surface coat, through two morphologically distinct forms in the fly and then they emerge as long, slender bloodstream forms, covered with a variant surface glycoprotein coat. Once inside the mammalian host, the long slender bloodstream form actively divides and establishes parasitemia. In the late phases of infection, the morphology of the parasite changes to nondividing short stumpy forms, which are ready to be taken up by the insect during a blood meal. The bloodstream form, with a rudimentary mitochondrion, is perfectly adapted to utilize the abundant supply of glucose from the mammalian blood and generate sufficient energy by glycolysis. The insect form, on the other hand, has a functional mitochondrion and generates most of its energy by respiration. These necessary metabolic adaptations depend upon a precise orchestration of numerous metabolic and cell biological activities.Studies of trypanosomes have uncovered several unusual biological phenomena (6). Notable among them are trans splicing and RNA editing (reviewed in references 7, 35, 46, 48, and 59). Protein-coding genes in trypanosomes are transcribed as long polycistronic precursor RNAs. Individual mature mRNAs are formed by trans splicing of a 39-nucleotide spliced leader (SL) RNA at the 5Ј end and subsequent 3Ј end maturation. RNA editing, used to produce mitochondrial mRNA, requires extensive alterations of primary transcripts by guide RNAs. Although guide RNA-dependent RNA editing is uniquely observed in trypanosomes, trans splicing has subsequently been observed in several other lower eukaryotes, including nematodes, trematodes, euglenoids, and chordates. The...

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Histone H2AZ dimerizes with a novel variant H2B and is enriched at repetitive DNA inTrypanosoma brucei

Cited by 70 publications

References 55 publications

Cell Biology of the Trypanosome Genome

Cell Biology of the Trypanosome Genome

Chromatin-Mediated Epigenetic Regulation in the Malaria Parasite Plasmodium falciparum

RNA Polymerase Transcription Machinery in Trypanosomes

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