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 Bioljournal_title
Molecular and cellular biologyauthors
Ekanayake DK,Minning T,Weatherly B,Gunasekera K,Nilsson D,Tarleton R,Ochsenreiter T,Sabatini Rdoi
10.1128/MCB.01277-10subject
Has Abstractpub_date
2011-04-01 00:00:00pages
1690-700issue
8eissn
0270-7306issn
1098-5549pii
MCB.01277-10journal_volume
31pub_type
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