Mapping of Long-Range Associations throughout the Fission Yeast Genome Reveals Global Genome Organization Linked to Transcriptional Regulation

The Wistar Institute, Philadelphia, Pennsylvania, USA.
Nucleic Acids Research (Impact Factor: 9.11). 10/2010; 38(22):8164-77. DOI: 10.1093/nar/gkq955
Source: PubMed


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.

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Available from: Hideki Tanizawa, Jan 15, 2014
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    • "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 (Dixon et al., 2012; 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. "
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    • "Normalized contact count and confidence score matrices exhibit a canonical ''X'' shape, indicative of a folded chromosome architecture anchored at the centromere, as previously observed in yeast (Duan et al. 2010; Tanizawa et al. 2010) and the bacterium C. crescentus (Fig. 1C,D; Supplemental Fig. 3; Umbarger et al. 2011). However, chromosomes that harbor nonsubtelomeric clusters of genes involved in antigenic variation and immune evasion (Supplemental File 3) (VRSM genes: var, rifin, stevor and Pfmc-2tm)—chromosomes 4, 6, 7, 8, and 12—exhibit additional folding structure (Fig. 1C,D; Supplemental Fig. 3). "
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    • "Consequently, they simply discarded all proximal and a large portion of mid-range contacts, focusing instead on distal and interchromosomal contacts. Tanizawa et al. (2010) analyzed mid-range contacts in fission yeast by first normalizing the observed contact counts with respect to an experimental control and then correcting for random polymer looping using a double-exponential curve fitting procedure. Sexton et al. (2012) proposed a hierarchical domain model for the Drosophila genome that infers an expected chromosomal contact matrix at 10-kb resolution for each chromosome . "
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