Eukaryotic genomes are non-randomly organized in the nucleus. It is becoming clear that intra-nuclear positions of genomic loci are influenced by various nuclear processes including transcription, replication and repair (1
). It is well known that the ribosomal genes (rDNA repeats) are transcribed by RNA polymerase (Pol) I in the nucleolus. Moreover, it has been shown that Pol III genes such as tRNA genes are clustered at or near the nucleolus in yeasts, suggesting that Pol III transcription likely occurs in a subnuclear domain (2
). It has been proposed that Pol II gene transcription involves higher-order genome organization associated with ‘transcription factories’ which accumulate Pol II transcription machinery for gene transcription (4–7
). It has recently been suggested that transcription factors are involved in the association of genes with these transcription factories (8
). However, how transcription factories function remains unclear, partly because they have been studied in complex mammalian cells. Studying the factories in a model organism with a much simpler genome can facilitate understanding of the role of transcription factories with regard to transcriptional regulation.
Fluorescent in situ
hybridization (FISH) has been used to analyze nuclear localization of genomic loci at a global level, but a relatively new approach, chromosome conformation capture (3C), now allows us to investigate physical associations between specific genomic loci (9
). The use of the 3C method has triggered development of several additional genome-wide approaches including 4C and 5C (10–12
). It has recently been reported that 3C combined with next-generation DNA sequencing, referred to as Hi-C, can be used to comprehensively map genomic associations (13
). Application of the Hi-C method to the human genome has identified genomic associations at a resolution of 1
Mb, and has shown that the human genome is segregated into two compartments corresponding to open and closed chromatin. We hypothesized that the latest genomics approach was likely to provide much higher-resolution if applied to a model organism carrying a small genome. Indeed, the similar method applied to budding yeast significantly increased the resolution of mapped genomic associations (14
The fission yeast Schizosaccharomyces pombe
offers an excellent model system to investigate the organization of a functional genome. Its genome is ~14 Mb, consisting of ~5000 genes located on only three chromosomes, with an organization and composition similar to higher eukaryotes (16
). For example, its genome contains large stretches of heterochromatin at centromeres and subtelomeres (17
). We have previously shown that the fission yeast genome displays a specific functional architecture within the nucleus (2
In this study, we utilize the latest genomic approach combining the 3C and next-generation DNA sequencing to gain insights into functional relationships between the global genome organization and transcriptional regulation in the model organism fission yeast. Our analyses have revealed significant associations between highly transcribed genes, between co-regulated genes during cell-cycle progression, and between functionally related genes derived from particular gene ontology groups. Our study identifies inter- and intra-chromosomal interactions providing further evidence for a mechanism of functional genome organization that supports gene expression in a structure similar to the transcription factory described in mammals.