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

Respuela, Patricia; Ferella, Marcela; Rada-Iglesias, Álvaro; Åslund, Lena

doi:10.1074/jbc.m802081200

Cited by 97 publications

(100 citation statements)

References 55 publications

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“…The lack of an extensive basic surface on trypanosome TFIIB may reflect a relaxed specificity of tRNAP-II orientation at promoters in trypanosomes. Most trypanosome protein-encoding genes are transcribed in large arrays that appear to initiate bidirectionally from strand switch regions (35)(36)(37). Weak specificity of preinitiation complex orientation could cause bidirectional transcription from strand switch regions.…”

Section: Discussionmentioning

confidence: 99%

Structure of the C-terminal domain of transcription factor IIB from Trypanosoma brucei

Ibrahim¹,

Kanneganti²,

Rieckhof

et al. 2009

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

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In trypanosomes, the production of mRNA relies on the synthesis of the spliced leader (SL) RNA. Expression of the SL RNA is initiated at the only known RNA polymerase II promoter in these parasites. In the pathogenic trypanosome, Trypanosoma brucei, transcription factor IIB (tTFIIB) is essential for SL RNA gene transcription and cell viability, but has a highly divergent primary sequence in comparison to TFIIB in well-studied eukaryotes. Here we describe the 2.3 Å resolution structure of the C-terminal domain of tTFIIB (tTFIIB C ). The tTFIIB C structure consists of 2 closely packed helical modules followed by a C-terminal extension of 32 aa. Using the structure as a guide, alanine substitutions of basic residues in regions analogous to functionally important regions of the well-studied eukaryotic TFIIB support conservation of a general mechanism of TFIIB function in eukaryotes. Strikingly, tTFIIB C contains additional loops and helices, and, in contrast to the highly basic DNA binding surface of human TFIIB, contains a neutral surface in the corresponding region. These attributes probably mediate trypanosomespecific interactions and have implications for the apparent bidirectional transcription by RNA polymerase II in protein-encoding gene expression in these organisms.eukaryotic transcription ͉ parasite ͉ RNA polymerase II ͉ trypanosome T rypanosomes are flagellated protozoa, belonging to the order Kinetoplastida, that are exclusively parasitic (1). These organisms reside in insect vectors that transmit the parasites to mammals, birds, fish, and plants. Trypanosoma brucei and Trypanosoma cruzi are of particular medical concern because they cause debilitating and fatal diseases in millions of people annually in tropical regions of the world (2). Trypanosomes diverged from other eukaryotes early in evolution, and thus many biological processes that are well understood in metazoans are highly distinct in these parasites (3, 4). For example, little is known about how trypanosome RNA polymerase II (tRNAP-II) transcription is initiated. It is known that tRNAP-II transcribes most protein-encoding genes, which are arranged in tandem arrays, into polycistronic mRNAs (5). Thus far, the only tRNAP-II promoter that has been identified is the spliced leader (SL) RNA gene promoter (6). The SL RNA gene codes for the SL, which is capped and added in a trans-splicing reaction to the 5Ј end of each ORF contained in a polycistronic mRNA. The addition of an SL to every mRNA is a universal requirement in trypanosomes; therefore, understanding transcription initiation at the SL RNA gene promoter is a crucial step toward understanding the control of tRNAP-II transcription in these parasites (4, 7).To date, components of the SL RNA transcriptional machinery have been studied by using genomics or biochemistry to identify candidate proteins followed by a combination of phenotypic analysis of protein function using either RNAi-silencing of endogenous protein in parasites or depletion/add back studies of in vitro transcription systems. T...

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Section: Discussionmentioning

confidence: 99%

Structure of the C-terminal domain of transcription factor IIB from Trypanosoma brucei

Ibrahim¹,

Kanneganti²,

Rieckhof

et al. 2009

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

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“…Antibodies against tagged H2AZ and H2BV gave peaks of enrichment coincident with antiH4K10ac, suggesting that transcription start sites are characterized by nucleosomes containing H2AZ, H2BV, and H4K10ac. Previous studies showed that H2BV-containing nucleosomes are enriched in trimethylated H3K4 (Mandava et al 2008) and that divergent SSRs are also enriched with acetylated H3 (Respuela et al 2008).…”

Section: Trypanosome Histone Variants and Transcriptionmentioning

confidence: 99%

“…Neighboring transcription units can be either convergent or divergent, and the regions between them are known as strand switch regions (SSRs). Nuclear runon assays in the related trypanosomatids Leishmania major and Trypanosoma cruzi, which are highly syntenic with T. brucei (El-Sayed et al 2005), showed that RNA polymerase II (pol II) transcription initiates at divergent SSRs and terminates at convergent SSRs (MartinezCalvillo et al 2003(MartinezCalvillo et al , 2004Respuela et al 2008). Trypanosome genomes, however, lack recognizable pol II promoter elements (Clayton 2002).…”

Section: Trypanosome Histone Variants and Transcriptionmentioning

confidence: 99%

Chromatin-based transcriptional punctuation: Figure 1.

Talbert

Henikoff²

2009

Genes Dev.

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The long polycistronic transcription units of trypanosomes do not appear to be demarcated by the usual DNA motifs that punctuate transcription in familiar eukaryotes. In this issue of Genes & Development, Siegel and colleagues (pp. 1063–1076) describe a system for the demarcation of trypanosome transcription units based on the deposition and turnover of histone variants rather than on the binding of transcription factors. Replication-independent incorporation of histone variants and destabilization of nucleosomes is an emerging theme at promoters of more familiar eukaryotes, and it now appears that this system is an evolutionarily conserved mode of transcriptional punctuation.

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“…It would be also interesting to analyze the genomic distribution of histone variants in Leishmania. In T. cruzi sequencing of DNA from ChIP experiments revealed that acetylated and methylated histones were found to be enriched in TSS but not in TTS [122].…”

Section: Molecular Interactions On Chipmentioning

confidence: 99%

Using Genomic Information to Understand Leishmania Biology

Toledo¹

2010

TOPARAJ

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Abstract:The genomes of different species of Leishmania have been deciphered in recent years. We learned that the genome content and organization of Leishmania major, Leishmania braziliensis and Leishmania infantum are highly similar and annotation of these genomes revealed that there are few species-specific genes. Association of genome information with reverse and forward genetics approaches allows posing and answering relevant biological questions in a novel way. In this article we briefly present an overview of relevant aspects of genome organization of the Leishmania and how this information can be used to improve our understanding of the biology, pathogenesis, host-parasite interaction issues. We present some of the most useful bioinformatics tools/softwares, which are currently available and how each one of them can be used to explore the genome supporting a wide variety of queries. We included other computational tools which allow integrating the genome data with biochemical pathways revealing metabolic and regulatory networks to be investigated. Finally, we discuss reverse and forward genetic tools available and finalize with considerations on established and novel high-throughput approaches at the genome, transcriptome and proteome levels.

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

Cited by 97 publications

References 55 publications

Structure of the C-terminal domain of transcription factor IIB from Trypanosoma brucei

Structure of the C-terminal domain of transcription factor IIB from Trypanosoma brucei

Chromatin-based transcriptional punctuation: Figure 1.

Using Genomic Information to Understand Leishmania Biology

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