Genome organization is a major component of gene expression control in response to stress and during the cell division cycle in
            <i>trypanosomes</i>

Kelly, Steven; Krämer, Susanne; Schwede, Angela; Maini, Philip K.; Gull, Keith; Carrington, Mark

doi:10.1098/rsob.120033

Cited by 38 publications

(42 citation statements)

References 33 publications

(57 reference statements)

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“…These findings are consistent with work by Kelly et al. that has indicated that the location of a gene within a PTU can impact its expression (56). Thus, regulated expression of genes within PTUs can be achieved through their spatial organization and position relative to base J.…”

Section: Discussionmentioning

confidence: 99%

Regulation of transcription termination by glucosylated hydroxymethyluracil, base J, in Leishmania major and Trypanosoma brucei

Reynolds

Cliffe

Förstner³

et al. 2014

Nucleic Acids Research

143

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Base J, β-d-glucosyl-hydroxymethyluracil, is an epigenetic modification of thymine in the nuclear DNA of flagellated protozoa of the order Kinetoplastida. J is enriched at sites involved in RNA polymerase (RNAP) II initiation and termination. Reduction of J in Leishmania tarentolae via growth in BrdU resulted in cell death and indicated a role of J in the regulation of RNAP II termination. To further explore J function in RNAP II termination among kinetoplastids and avoid indirect effects associated with BrdU toxicity and genetic deletions, we inhibited J synthesis in Leishmania major and Trypanosoma brucei using DMOG. Reduction of J in L. major resulted in genome-wide defects in transcription termination at the end of polycistronic gene clusters and the generation of antisense RNAs, without cell death. In contrast, loss of J in T. brucei did not lead to genome-wide termination defects; however, the loss of J at specific sites within polycistronic gene clusters led to altered transcription termination and increased expression of downstream genes. Thus, J regulation of RNAP II transcription termination genome-wide is restricted to Leishmania spp., while in T. brucei it regulates termination and gene expression at specific sites within polycistronic gene clusters.

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Section: Discussionmentioning

confidence: 99%

Regulation of transcription termination by glucosylated hydroxymethyluracil, base J, in Leishmania major and Trypanosoma brucei

Reynolds

Cliffe

Förstner³

et al. 2014

Nucleic Acids Research

143

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show abstract

“…Analysis of the T. brucei transcriptome revealed that RNA polymerase II (pol II) transcription initiates bidirectionally from putative pol II transcription start sites (TSS) at divergent SSRs, as well as a number of positions internal to PTUs [12,13]. Although all genes in a PTU are constitutively expressed, the location of a gene within the PTU was shown to impact on the transcript level of that gene [14]. …”

Section: Genome Organisationmentioning

confidence: 99%

The epigenome of Trypanosoma brucei: A regulatory interface to an unconventional transcriptional machine

Maree

Patterton

2014

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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The epigenome represents a major regulatory interface to the eukaryotic genome. Nucleosome positions, histone variants, histone modifications and chromatin associated proteins all play a role in the epigenetic regulation of DNA function. Trypanosomes, an ancient branch of the eukaryotic evolutionary lineage, exhibit some highly unusual transcriptional features, including the arrangement of functionally unrelated genes in large, polymerase II transcribed polycistronic transcription units, often exceeding hundreds of kilobases in size. It is generally believed that transcription initiation plays a minor role in regulating the transcript level of genes in trypanosomes, which are mainly regulated post-transcriptionally. Recent advances have revealed that epigenetic mechanisms play an essential role in the transcriptional regulation of Trypanosoma brucei. This suggested that the modulation of gene activity, particularly that of pol I transcribed genes, is, indeed, an important control mechanism, and that the epigenome is critical in regulating gene expression programs that allow the successful migration of this parasite between hosts, as well as the continuous evasion of the immune system in mammalian hosts. A wide range of epigenetic signals, readers, writers and erasers have been identified in trypanosomes, some of which have been mapped to essential genetic functions. Some epigenetic mechanisms have also been observed to be unique to trypanosomes. We review recent advances in our understanding of epigenetic control mechanisms in T. brucei, the causative agent of African sleeping sickness, and highlight the utility of epigenetic targets in the possible development of new therapies for human African trypanosomiasis.

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“…For example, distance from TSS regions is known to influence gene expression levels in T. brucei (29). Our data show that the steady state levels of the genes far away from TSS regions appear to be increased (see Figure 2A and B) in mutant cells compared to wild type cells.…”

Section: Discussionmentioning

confidence: 99%

An essential domain of an early-diverged RNA polymerase II functions to accurately decode a primitive chromatin landscape

Das

Banday

Fisher

et al. 2017

Nucleic Acids Research

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A unique feature of RNA polymerase II (RNA pol II) is its long C-terminal extension, called the carboxy-terminal domain (CTD). The well-studied eukaryotes possess a tandemly repeated 7-amino-acid sequence, called the canonical CTD, which orchestrates various steps in mRNA synthesis. Many eukaryotes possess a CTD devoid of repeats, appropriately called a non-canonical CTD, which performs completely unknown functions. Trypanosoma brucei, the etiologic agent of African Sleeping Sickness, deploys an RNA pol II that contains a non-canonical CTD to accomplish an unusual transcriptional program; all protein-coding genes are transcribed as part of a polygenic precursor mRNA (pre-mRNA) that is initiated within a several-kilobase-long region, called the transcription start site (TSS), which is upstream of the first protein-coding gene in the polygenic array. In this report, we show that the non-canonical CTD of T. brucei RNA pol II is important for normal protein-coding gene expression, likely directing RNA pol II to the TSSs within the genome. Our work reveals the presence of a primordial CTD code within eukarya and indicates that proper recognition of the chromatin landscape is a central function of this RNA pol II-distinguishing domain.

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Genome organization is a major component of gene expression control in response to stress and during the cell division cycle in trypanosomes

Cited by 38 publications

References 33 publications

Regulation of transcription termination by glucosylated hydroxymethyluracil, base J, in Leishmania major and Trypanosoma brucei

Regulation of transcription termination by glucosylated hydroxymethyluracil, base J, in Leishmania major and Trypanosoma brucei

The epigenome of Trypanosoma brucei: A regulatory interface to an unconventional transcriptional machine

An essential domain of an early-diverged RNA polymerase II functions to accurately decode a primitive chromatin landscape

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