Base J and H3.V Regulate Transcriptional Termination in Trypanosoma brucei

PLoS Genetics
Danae SchulzHee-Sook Kim

Abstract

Trypanosoma brucei is a protozoan parasite that lacks many transcription factors found in other eukaryotes, such as those whose binding demarcates enhancers. T. brucei retains histone variants and modifications, however, and it is hypothesized that it relies on epigenetic marks to define transcription-related boundaries. The histone H3 variant (H3.V) and an alternate nucleotide, base J (ß-D-glucosyl-hydroxymethyluracil), are two chromatin marks found at both transcription termination sites (TTSs) and telomeres. Here, we report that the absence of both base J and H3.V result in transcription readthrough and the appearance of antisense transcripts near TTSs. Additionally, we find that maintaining the transcriptional silencing of pol I-transcribed telomeric Variant Surface Glycoprotein (VSG) genes appears to be dependent on deposition of H3.V alone. Our study reveals that gene expression depends on different epigenetic cues depending on chromosomal location and on the transcribing polymerase. This work provides insight into how these signals may have evolved into the more nuanced and fine-tuned gene regulatory mechanisms observed in other model systems.

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Citations

May 27, 2016·Proceedings of the National Academy of Sciences of the United States of America·Lucy GloverDavid Horn
Jun 19, 2016·Proceedings of the National Academy of Sciences of the United States of America·Danae Schulz, F Nina Papavasiliou
Sep 25, 2017·Angewandte Chemie·Thomas CarellFabio Spada
Feb 8, 2019·The Journal of Eukaryotic Microbiology·Carolina P BañuelosDaniel O Sánchez
Mar 22, 2020·Nature Communications·Amelie J KrausT Nicolai Siegel
Nov 5, 2019·Journal of Molecular Biology·Arpita SahaBibo Li
Dec 22, 2017·Emerging Topics in Life Sciences·Cher-Pheng Ooi, Gloria Rudenko

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Methods Mentioned

BETA
immunoprecipitation
glucosylation
RNA-seq
Magnetic
flow cytometry
PCR

Software Mentioned

Bowtie
matplotlib
R
R Foundation for Statistical Computing

Related Concepts

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African trypanosomiasis, also known as sleeping sickness, is an insect-borne parasitic disease of humans and other animals. It is caused by protozoa of the species Trypanosoma brucei and almost invariably progresses to death unless treated. Discover the latest research on African trypanosomiasis here.