title: Genome-wide analysis reveals extensive functional interaction between DNA replication initiation and transcription in the genome of Trypanosoma brucei.
abstract: 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.
authors: The Wellcome Trust Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences, Institute of Infection, Immunity and Inflammation, University of Glasgow, Sir Graeme Davies Building, 120 University Place, Glasgow G12 8TA, UK.
authors: Calvin
authors: C
authors: Tiengwe
authors: Lucio
authors: L
authors: Marcello
authors: Helen
authors: H
authors: Farr
authors: Nicholas
authors: N
authors: Dickens
authors: Steven
authors: S
authors: Kelly
authors: Michal
authors: M
authors: Swiderski
authors: Diane
authors: D
authors: Vaughan
authors: Keith
authors: K
authors: Gull
authors: J David
authors: JD
authors: Barry
authors: Stephen D
authors: SD
authors: Bell
authors: Richard
authors: R
authors: McCulloch
mesh_terms: D001665:Binding Sites / Q000235:genetics; D004261:DNA Replication / Q000235:genetics*; D004843:Epistasis, Genetic; D005786:Gene Expression Regulation; D018503:Genome, Protozoan / Q000235:genetics; D008954:Models, Biological; D051738:Origin Recognition Complex / Q000032:analysis / Q000378:metabolism; D018741:Replication Origin / Q000235:genetics / Q000502:physiology*; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic / Q000235:genetics*; D014346:Trypanosoma brucei brucei / Q000235:genetics*
chemical_list: D051738:Origin Recognition Complex