TY - JOUR
T1 - Genome-wide Analysis Reveals Extensive Functional Interaction between DNA Replication Initiation and Transcription in the Genome of Trypanosoma brucei
AU - Tiengwe, Calvin
AU - Marcello, Lucio
AU - Farr, Helen
AU - Dickens, Nicholas
AU - Kelly, Steven
AU - Swiderski, Michal
AU - Vaughan, Diane
AU - Gull, Keith
AU - Barry, J. david
AU - Bell, Stephen d.
AU - Mcculloch, Richard
N1 - © 2012 The Authors. Published by Elsevier Inc.
PY - 2012/7/12
Y1 - 2012/7/12
N2 - Identification of replication initiation sites, termed origins, is a crucial step in understanding genome transmission in any organism. Transcription of the Trypanosoma brucei genome is highly unusual, with each chromosome comprising a few discrete transcription units. To understand how DNA replication occurs in the context of such organization, we have performed genome-wide mapping of the binding sites of the replication initiator ORC1/CDC6 and have identified replication origins, revealing that both localize to the boundaries of the transcription units. A remarkably small number of active origins is seen, whose spacing is greater than in any other eukaryote. We show that replication and transcription in T. brucei have a profound functional overlap, as reducing ORC1/CDC6 levels leads to genome-wide increases in mRNA levels arising from the boundaries of the transcription units. In addition, ORC1/CDC6 loss causes derepression of silent Variant Surface Glycoprotein genes, which are critical for host immune evasion.
AB - Identification of replication initiation sites, termed origins, is a crucial step in understanding genome transmission in any organism. Transcription of the Trypanosoma brucei genome is highly unusual, with each chromosome comprising a few discrete transcription units. To understand how DNA replication occurs in the context of such organization, we have performed genome-wide mapping of the binding sites of the replication initiator ORC1/CDC6 and have identified replication origins, revealing that both localize to the boundaries of the transcription units. A remarkably small number of active origins is seen, whose spacing is greater than in any other eukaryote. We show that replication and transcription in T. brucei have a profound functional overlap, as reducing ORC1/CDC6 levels leads to genome-wide increases in mRNA levels arising from the boundaries of the transcription units. In addition, ORC1/CDC6 loss causes derepression of silent Variant Surface Glycoprotein genes, which are critical for host immune evasion.
U2 - 10.1016/j.celrep.2012.06.007
DO - 10.1016/j.celrep.2012.06.007
M3 - Article
SN - 2211-1247
VL - 2
SP - 185
EP - 197
JO - Cell Reports
JF - Cell Reports
IS - 1
ER -