Epigenetic regulation of transcription and virulence in Trypanosoma cruzi by O-linked thymine glucosylation of DNA. Trypanosoma cruzi

Unlike other eukaryotes, the protein coding genes of Trypanosoma cruzi are arranged into large polycistronic gene clusters transcribed by polymerase II (Pol II). Thus, trypanosomes rely on post-transcriptional processes to regulate gene expression. Here, we show that the glucosylated thymine DNA base (-D-glucosyl hydroxymethyluracil or base J) is present within sequences flanking the polycistronic units (PTU) in T. cruzi. loss of base J at sites of transcription initiation, via deletion of the two enzymes that regulate J synthesis (JBP1 and JBP2), correlates with an increased rate of Pol II transcription and subsequent genome-wide increase in gene expression. genes include virulence genes and the resulting parasites are defective in host cell invasion and egress. These studies indicate that base J represents an epigenetic factor regulating Pol II transcription initiation in kinetoplastids, and provides the first biological role of the only hyper-modified DNA base in eukaryotes. This entry contains the results using SLT, digital gene expression profiling of tags read off the spliced leader sequence of all mature trypanosomatid messages, for the life-cycle of T. cruzi, four stages, in wild-type as well as JBP1 KO cells. Overall design: This entry contains the results using SLT, digital gene expression profiling of tags read off the spliced leader sequence of all mature trypanosomatid messages, for the life-cycle of T. cruzi, four stages, in wild-type as well as JBP1 KO cells, for eight libraries in total.