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Title: Preferential associations between actively transcribing genes reveal distinct transcriptional networks
Author: Horton, A. M.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2006
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Active genes are associated with ‘transcription factories’ which are discrete foci of nascent RNA production and high levels of RNA polymerase II. Actively transcribed genes located on the same chromosome dynamically co-localise to the same transcription factory at high frequencies. Can genes in trans also share multi-gene transcription factories? To address this question I studied the mutual positioning of several genes on mouse chromosomes 7 and 11 by Chromosome Conformation Capture (3C) and RNA fluorescent in situ hybridisation (RNA FISH). The 3C technique generates a population-average measurement of juxtaposition frequency between any two genomic loci, thus providing information on their relative proximity in the nucleus, while RNA FISH allows the visualisation of individual loci at the single-cell level. Erythroid-specific 3C products were detected between Hbb (chr. 7) and Hba (chr. 11), and between Hbb (chr. 7) and Slc4a (chr. 11). These results were confirmed by RNA FISH which showed co-localisation between Hbb and either Hba or Slc4a occurred at frequencies above those expected for random association of active alleles. Therefore, genes from different chromosomes can co-occupy the same transcription factory. Moreover, each gene pair shows a characteristic co-localisation frequency; individual genes co-associate with preferred partners. These data reveal physical transcription networks of co-regulated genes and indicate that transcription factories are major focal points for the non-random nuclear organisation of the genome.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available