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

Abstract

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.

Fluorescence‐based assay for accurate measurement of transcriptional activity in trypanosomatid parasites

“…However, trypanosomatids lack classic RNA polymerase II promoters for protein-coding genes, and the promoter sequence is undefined (6). Some studies have shown that transcription initiates at chromosome regions called strand-switch regions (10,11) and that transcription initiation seems to be regulated by an epigenetic mechanism (12)(13)(14)(15)(16)(17)(18). Some studies have shown that transcription initiates at chromosome regions called strand-switch regions (10,11) and that transcription initiation seems to be regulated by an epigenetic mechanism (12)(13)(14)(15)(16)(17)(18).…”

“…While in other eukaryotes, transcription is monocistronic and mRNAs are processed by cis-splicing, in trypanosomatids, long polycistronic transcription units of RNA are transcribed by polymerase II and processed by trans splicing and polyadenylation to produce the mature mRNA (8,9). Some studies have shown that transcription initiates at chromosome regions called strand-switch regions (10,11) and that transcription initiation seems to be regulated by an epigenetic mechanism (12)(13)(14)(15)(16)(17)(18).…”

Trypanosoma cruzi senses intracellular heme levels and regulates heme homeostasis by modulating TcHTE protein expression

“…Or, they could be an essential component of a heteromeric complex responsible for heme transport activity. Moreover, considering that the gene expression in trypanosomatids is not regulated by canonical transcription factors (18,19), it is not clear how the expression of HRG genes is regulated by heme.…”

Caracterização bioquímica e biofísica de proteínas específicas envolvidas no SL <i>trans-splicing</i> de <i>Trypanosoma brucei</i>

“…Os minicromossomos abrigam um repertório de genes que codificam para VSG flanqueados por uma sequência repetitiva de 177 pares de base na região 5'. 23,27,[32][33] Vários aspectos da organização do genoma nuclear e regulação da expressão gênica de Cada gene individual é imediatamente seguido do próximo, podendo haver uma sequência intercistrônica de tamanho variável entre eles. 23,32 C A P Í T U L O 1 | 43 Figura 1.6 -Representação esquemática do genoma nuclear de T. brucei.…”

“…Em outros tripanossomatídeos, a terminação da transcrição parece estar associada à acumulação de um nucleotídeo modificado conhecido como J (β-Dglucopiranosiloximethiluracila). [32][33]39 A enzima RNA polimerase I transcreve não apenas as moléculas de RNA ribossomal (rRNA) como também genes que codificam para VSG e prociclina. Já a enzima RNA polimerase III transcreve um pequeno número de RNAs que são codificadores para proteínas que atuam no processo de tradução (tRNAs e rRNAs 5S), processamento de mRNA (snRNAs U1, U2, U4 e U5, que serão detalhados posteriormente) e outros processos celulares (como o RNA 7SL).…”