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Title: Epigenetic regulation of transcription and virulence of Trypanosoma cruzi      
availability:
available
aggregation:
instance of dataset
privacy:
not applicable
refinement:
curated
dateReleased:
05-01-2014
ID:
E-GEOD-23855
description:
Trypanosoma cruzi, a flagellated protozoan, is the causative agent of Chagas’ disease, a chronic and potentially fatal disease that causes irreversible damage to heart and digestive tract in humans. Like all trypanosomes, the protein coding genes of T. cruzi are arranged into large polycistronic gene clusters transcribed by polymerase II (Pol II). Therefore, trypanosomes presumably rely on post-transcriptional process to regulate gene expression. Pol II promoters have not been identified and there is no evidence for regulated gene expression at the transcriptional level. However, the presence of the hyper-modified DNA base J, Beta-D-glucosyl hydroxymethyluracil, at regions flanking the polycistronic units (PTU) in T. brucei suggested its involvement in regulating Pol II transcription. We now demonstrate that base J is localized at PTU flanking regions in T. cruzi and levels are differentially regulated by the thymidine hydroxylases, JBP1 and JBP2, involved in J biosynthesis. Microarray analysis of the JBP1dKO and JBP2dKO indicate the up and down regulation of several hundred genes distributed throughout the genome. We show a large increase in Pol II transcription rate following the decrease in base J at the PTU flanks. Changes in gene expression include virulence genes and parasites are defective in host cell invasion and egress. There is a direct correlation between the reduction in base J levels, number of genes affected and strength of the virulence phenotype. These studies indicate that base J represents an epigenetic factor regulating Pol II transcription initiation in kinetoplastids and provides a biological role of the only hyper-modified DNA base in eukaryotes. J1 and J2 null mutant trypomastigotes were each compared to wild type trypomastigotes. There were 3 biological replicates for each comparison.
keywords:
transcription profiling by array
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storedIn:
Array Express
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accessType:
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primary:
true
accessURL: https://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-23855
format:
JSON
storedIn:
OmicsDI
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not compressed
accessType:
download
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primary:
false
accessURL: www.omicsdi.org/ws/dataset/arrayexpress-repository/E-GEOD-23855.json
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XML
storedIn:
OmicsDI
qualifier:
not compressed
accessType:
download
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none
authentication:
none
primary:
false
accessURL: http://www.omicsdi.org/ws/dataset/arrayexpress-repository/E-GEOD-23855.xml
ID:
SCR:014747
name:
Omics Discovery Index
abbreviation:
OmicsDI
homePage: http://www.omicsdi.org/