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

Abstract:

:Unlike other eukaryotes, the protein-coding genes of Trypanosoma cruzi are arranged in large polycistronic gene clusters transcribed by polymerase II (Pol II). Thus, it is thought that trypanosomes rely solely on posttranscriptional processes to regulate gene expression. Here, we show that the glucosylated thymine DNA base (β-d-glucosyl-hydroxymethyluracil or base J) is present within sequences flanking the polycistronic units (PTUs) in T. cruzi. The loss of base J at sites of transcription initiation, via deletion of the two enzymes that regulate base J synthesis (JBP1 and JBP2), correlates with an increased rate of Pol II transcription and subsequent genome-wide increase in gene expression. The affected genes include virulence genes, and the resulting parasites are defective in host cell invasion and egress. These studies indicate that base J is an epigenetic factor regulating Pol II transcription initiation in kinetoplastids and provides the first biological role of the only hypermodified DNA base in eukaryotes.

journal_name

Mol Cell Biol

authors

Ekanayake DK,Minning T,Weatherly B,Gunasekera K,Nilsson D,Tarleton R,Ochsenreiter T,Sabatini R

doi

10.1128/MCB.01277-10

subject

Has Abstract

pub_date

2011-04-01 00:00:00

pages

1690-700

issue

8

eissn

0270-7306

issn

1098-5549

pii

MCB.01277-10

journal_volume

31

pub_type

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