Mapping of long-range associations throughout the fission yeast genome reveals global genome organization linked to transcriptional regulation

Abstract

We have comprehensively mapped long-range associations between chromosomal regions throughout the fission yeast genome using the latest genomics approach that combines next generation sequencing and chromosome conformation capture (3C). Our relatively simple approach, referred to as enrichment of ligation products (ELP), involves digestion of the 3C sample with a 4 bp cutter and self-ligation, achieving a resolution of 20 kb. It recaptures previously characterized genome organizations and also identifies new and important interactions. We have modeled the 3D structure of the entire fission yeast genome and have explored the functional relationships between the global genome organization and transcriptional regulation. We find significant associations among highly transcribed genes. Moreover, we demonstrate that genes co-regulated during the cell cycle tend to associate with one another when activated. Remarkably, functionally defined genes derived from particular gene ontology groups tend to associate in a statistically significant manner. Those significantly associating genes frequently contain the same DNA motifs at their promoter regions, suggesting that potential transcription factors binding to these motifs are involved in defining the associations among those genes. Our study suggests the presence of a global genome organization in fission yeast that is functionally similar to the recently proposed mammalian transcription factory.

Chromosome positioning and the clustering of functionally related loci in yeast is driven by chromosomal interactions

“…These single structures have been used to make inferences about the organization of the respective genomes. 6,9 Microscopic studies show considerable variation in the distances between pairs of loci within populations of cells 10,11,13 and…”

“…Single representations of the 3-dimensional organization of the Saccharomyces cerevisiae and Schizosaccharomyces pombe genomes have been generated using empirically obtained chromosomal interaction frequencies that were converted into linear distance approximations. 6,8,9 These studies resulted in the proposal of unique genome conformations that do not represent the dynamic nature of nuclear organization. However, it is important to incorporate dynamism because genome organization shows a lot of variability [10][11][12] indicating that it must change from cell to cell and over time.…”

The Role of Chromosome Domains in Shaping the Functional Genome

“…Evolution TAD organization appears to be a conserved, but not universal phenomenon (Table 1); TADs are readily observed in Drosophila (Hou et al, 2012;Sexton et al, 2012) and mammalian Nora et al, 2012) genomes but are less clearly defined in Arabidopsis (Feng et al, 2014;Grob et al, 2014), Plasmodium falciparum (Ay et al, 2014), and yeasts (Duan et al, 2010;Tanizawa et al, 2010). Although more systematic chromatin interaction maps of different organisms are required to make further conclusions, it is interesting that species with clear TAD genomic organization match those with conservation of the insulator protein CTCF (Heger et al, 2012), further supporting its role as a genomic architectural protein.…”

Transcriptional regulatory network shapes the genome structure ofSaccharomyces cerevisiae

“…These models, however, are not realistic enough to explain what we are learning from nuclei structures 27,28 and gene expression phenomena. 20,22,23 A more generalized looping model postulated by Bohn et al 12 well explained the chromosome as a looped polymer under all scales. Especially in prokaryotes, like E. coli, transcriptional regulation did modulate the genome structure, which is clearly seen from the study conducted by Fritsche et al 31 Modeling has been fruitful in addressing physical property of chromatin and genome architecture, but few efforts have been made to investigate a functional genome organization, especially for eukaryotes.…”

“…Studies on fission yeast (Schizosaccharomyces pombe) have shed light on this question. Tanizawa et al conducted a comprehensive chromosome contact screening on fission yeast 23 and observed that co-regulated genes display a tendency to move toward each other once activated concurrently. More interestingly, gene loci showing higher interaction probability share a consensus sequence on their promoter regions.…”