Genome-wide analysis reveals extensive functional interaction between DNA replication initiation and transcription in the genome of Trypanosoma brucei.
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 replicat...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Cell Press
2012
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| _version_ | 1826267096585076736 |
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| author | Tiengwe, C Marcello, L Farr, H Dickens, N Kelly, S Swiderski, M Vaughan, D Gull, K Barry, J Bell, S McCulloch, R |
| author_facet | Tiengwe, C Marcello, L Farr, H Dickens, N Kelly, S Swiderski, M Vaughan, D Gull, K Barry, J Bell, S McCulloch, R |
| author_sort | Tiengwe, C |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T20:48:58Z |
| format | Journal article |
| id | oxford-uuid:36ea4a04-65e1-421a-82c9-83d0bf750fba |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:48:58Z |
| publishDate | 2012 |
| publisher | Cell Press |
| record_format | dspace |
| spelling | oxford-uuid:36ea4a04-65e1-421a-82c9-83d0bf750fba2022-03-26T13:40:52ZGenome-wide analysis reveals extensive functional interaction between DNA replication initiation and transcription in the genome of Trypanosoma brucei.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:36ea4a04-65e1-421a-82c9-83d0bf750fbaEnglishSymplectic Elements at OxfordCell Press2012Tiengwe, CMarcello, LFarr, HDickens, NKelly, SSwiderski, MVaughan, DGull, KBarry, JBell, SMcCulloch, RIdentification 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. |
| spellingShingle | Tiengwe, C Marcello, L Farr, H Dickens, N Kelly, S Swiderski, M Vaughan, D Gull, K Barry, J Bell, S McCulloch, R Genome-wide analysis reveals extensive functional interaction between DNA replication initiation and transcription in the genome of Trypanosoma brucei. |
| title | Genome-wide analysis reveals extensive functional interaction between DNA replication initiation and transcription in the genome of Trypanosoma brucei. |
| title_full | Genome-wide analysis reveals extensive functional interaction between DNA replication initiation and transcription in the genome of Trypanosoma brucei. |
| title_fullStr | Genome-wide analysis reveals extensive functional interaction between DNA replication initiation and transcription in the genome of Trypanosoma brucei. |
| title_full_unstemmed | Genome-wide analysis reveals extensive functional interaction between DNA replication initiation and transcription in the genome of Trypanosoma brucei. |
| title_short | Genome-wide analysis reveals extensive functional interaction between DNA replication initiation and transcription in the genome of Trypanosoma brucei. |
| title_sort | genome wide analysis reveals extensive functional interaction between dna replication initiation and transcription in the genome of trypanosoma brucei |
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