Chromatin-based transcriptional punctuation: Figure 1.

Talbert, Paul B.; Henikoff, Steven

doi:10.1101/gad.1806409

Cited by 18 publications

(15 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The histone variants H3V and H4V were mapped to RNAPII transcription termination sites. These data have led to the speculation that these different epigenetic marks rather than transcription factor binding could demarcate T. brucei transcription units [41] An additional epigenetic feature, the modified DNA base called 'J' has been found to be preferentially located at these RNAPII strand-switch regions [42]. Base J is an unusual glucosylated base (β-d-glucopyranosyloxymethyluracil) found in kinetoplastid protozoa, where it is invariably present at telomeres [43].…”

Section: The Unusual Architecture Of the Trypanosome Genomementioning

confidence: 97%

African trypanosomes: the genome and adaptations for immune evasion

Rudenko

2011

Essays in Biochemistry

View full text Add to dashboard Cite

The African trypanosome Trypanosoma brucei is a flagellated unicellular parasite transmitted by tsetse flies that causes African sleeping sickness in sub-Saharan Africa. Trypanosomes are highly adapted for life in the hostile environment of the mammalian bloodstream, and have various adaptations to their cell biology that facilitate immune evasion. These include a specialized morphology, with most nutrient uptake occurring in the privileged location of the flagellar pocket. In addition, trypanosomes show extremely high rates of recycling of a protective VSG (variant surface glycoprotein) coat, whereby host antibodies are stripped off of the VSG before it is re-used. VSG recycling therefore functions as a mechanism for cleaning the VSG coat, allowing trypanosomes to survive in low titres of anti-VSG antibodies. Lastly, T. brucei has developed an extremely sophisticated strategy of antigenic variation of its VSG coat allowing it to evade host antibodies. A single trypanosome has more than 1500 VSG genes, most of which are located in extensive silent arrays. Strikingly, most of these silent VSGs are pseudogenes, and we are still in the process of trying to understand how non-intact VSGs are recombined to produce genes encoding functional coats. Only one VSG is expressed at a time from one of approximately 15 telomeric VSG ES (expression site) transcription units. It is becoming increasingly clear that chromatin remodelling must play a critical role in ES control. Hopefully, a better understanding of these unique trypanosome adaptations will eventually allow us to disrupt their ability to multiply in the mammalian bloodstream.

show abstract

Section: The Unusual Architecture Of the Trypanosome Genomementioning

confidence: 97%

African trypanosomes: the genome and adaptations for immune evasion

Rudenko

2011

Essays in Biochemistry

View full text Add to dashboard Cite

show abstract

“…T. brucei encodes two H3 histones, H3 and the variant H3.V, which shares ~60% identity [94,95]. T. brucei appears to lack a centromere-specific CenH3 orthologue [95,96].…”

Section: Histone Variantsmentioning

confidence: 99%

“…T. brucei appears to lack a centromere-specific CenH3 orthologue [95,96]. H3.V was found to be highly enriched at telomeric repeats and subtelomeric regions (see Figure 2), but not at the 177 bp minichromosome repeat or 5S rDNA loci [94].…”

Section: Histone Variantsmentioning

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

View full text Add to dashboard Cite

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.

show abstract

“…Only trypanosomatids rely largely on chromatin, and in particular, on variations in nucleosome compositions, [162,156] to regulate gene epxression. In nearly all organisms, the local chromatin composition sets the stage for further, more specific mechanisms of regulation, such as sequence-specific transcription factors [97].…”

Section: The Regulation Of Transcription By Chromatinmentioning

confidence: 99%

Innovation in gene regulation: The case of chromatin computation

Prohaska

Stadler

Krakauer

2010

Journal of Theoretical Biology

View full text Add to dashboard Cite

Chromatin regulation is understood to be one of the fundamental modes of gene regulation in eukaryotic cells. We argue that the basic proteins that determine the chromatin architecture constitute an evolutionary ancient layer of transcriptional regulation common to all three domains of life. We explore phylogenetically, sources of innovation in chromatin regulation, focusing on protein domains related to chromatin structure and function, demonstrating a step-wise increase of complexity in chromatin regulation. Building upon the highly conserved use of variants of chromosomal architectural proteins to distinguish chromosomal states, Eukarya secondarily acquired mechanisms for "writing" chemical modifications onto chromatin that constitute persistent signals. The acquisition of reader domains enabled decoding of these complex, signal combinations and a decoupling of the signal from immediate biochemical effects. We show how the coupling of reading and writing, which is most prevalent in crown-group Eukarya, could have converted chromatin into a powerful computational device capable of storing and processing more information than pure cis-regulatory networks.Key words: Chromatin, gene regulation, evolution Summary of Findings and Evolutionary HypothesisGene regulation in extant organisms is a complex adaptive system making use of a diversity of mechanisms to ensure that proteins and complementary macromolecular components are produced and maintained at functional levels in variable environments.In this contribution we focus on one key regulatory subsystem of the cell: chromatin regulation. We argue that chromatin functioned as general regulator of transcription in the primordial nucleus, and that a series of key molecular innovations has significantly expanded the regulatory scope of the cell. In this section we summarize the key empirical results of the paper. Sections 2 through 6 provide the empirical support for these claims. In section 7, we formulate an evolutionary Email addresses: sonja@bioinf.uni-leipzig.de (Sonja J. Prohaska), studla@bioinf.uni-leipzig.de (Peter F. Stadler), krakauer@santafe.edu (David C. Krakauer) hypothesis that seeks to explain our findings in terms of the evolution of proto-genetic regulation. We then interpret this evolutionary sequence in terms of increasing computational power by locating key stages of the evolutionary sequence within a formal model of computation. Since sections 2-6 are primarily concerned with presenting evidence, those interested in the conceptual development of the argument can focus on sections 7 and 8.Two variants of Chromosomal Architectural Proteins (ChAPs) are sufficient to define binary genomic, and potentially phenotypic, states. We show how extensions to this binary system lead to potential distinctions among an increasing number of genomic states, culminating in forms of control localized to specific sites in the genome, as illustrated for example by extant mammalian histone variants capable of differential expression and/or localization to r...

show abstract

Chromatin-based transcriptional punctuation: Figure 1.

Cited by 18 publications

References 41 publications

African trypanosomes: the genome and adaptations for immune evasion

African trypanosomes: the genome and adaptations for immune evasion

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

Innovation in gene regulation: The case of chromatin computation

Contact Info

Product

Resources

About