Genome-wide analysis reveals extensive functional interaction between DNA replication initiation and transcription in the genome of trypanosoma brucei

Tiengwe, C. et al. (2012) Genome-wide analysis reveals extensive functional interaction between DNA replication initiation and transcription in the genome of trypanosoma brucei. Cell Reports, 2(1), pp. 185-197. (doi: 10.1016/j.celrep.2012.06.007)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Marcello, Dr Lucio and Dickens, Dr Nicholas and Bell, Mr Stephen and Barry, Professor J and Vaughan, Ms Diane and McCulloch, Professor Richard and Swiderski, Dr Michal
• Authors: Tiengwe, C., Marcello, L., Farr, H., Dickens, N.J., Kelly, S., Swiderski, M., Vaughan, D., Gull, K., Barry, J.D., Bell, S.D., and McCulloch, R.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Cell Reports
• ISSN: 2211-1247
• ISSN (Online): 2211-1247
• Copyright Holders: Copyright © 2012 The Authors
• First Published: First published in Cell Reports 2(1):185-197
• Publisher Policy: Reproduced under a Creative Commons License