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.

The authors show that Pol III transcribed genes such as tRNA and 5S rRNA genes localize to centromeres in fission yeast. The centromeric localization of Pol III genes is mediated by condensin. This study suggests that there is a functional link between the centromeric localization of dispersed Pol III genes and mitotic chromosome condensation.

In senescence, specific genes encoding secreted factors are excluded from senescence-associated heterochromatin foci, but the mechanisms underlying this senescence-associated secretory phenotype (SASP) are unclear. Aird et al. show that the chromatin-bound protein HMGB2 orchestrates the SASP by preventing heterochromatin spreading to these specific loci.

It is becoming clear that Structural Maintenance of Chromosomes (SMC) complexes, such as condensin and cohesin, are involved in the three-dimensional genome organization, yet the exact roles of these complexes in the functional organization remain unclear. This study employs the ChIA-PET approach to comprehensively identify genome-wide associations mediated by condensin and cohesin in fission yeast. We find that although cohesin and condensin often bind to the same loci, they direct different association networks and generate small and larger chromatin domains, respectively. Cohesin mediates local associations between loci positioned within 100 kb; condensin can drive longer-range associations. Moreover, condensin, but not cohesin, connects cell cycle-regulated genes bound by mitotic transcription factors. This study describes the different functions of condensin and cohesin in genome organization and how specific transcription factors function in condensin loading, cell cycle-dependent genome organization, and mitotic chromosome organization to support faithful chromosome segregation.

SUMMARY Complex genome organizations participate in various nuclear processes including transcription, DNA replication and repair. However, the mechanisms that generate and regulate these functional genome structures remain largely unknown. Here, we describe how the Ku heterodimer complex, which functions in nonhomologous end joining, mediates clustering of long terminal repeat (LTR) retrotransposons at centromeres in fission yeast. We demonstrate that the CENP-B subunit, Abp1, functions as a recruiter of the Ku complex, which in turn loads the genome-organizing machinery condensin to retrotransposons. Intriguingly, histone H3 Lys56 (H3K56) acetylation, which functions in DNA replication and repair, interferes with Ku localization at retrotransposons without disrupting Abp1 localization and, as a consequence, dissociates condensin from retrotransposons. This dissociation releases condensin-mediated genomic associations during S phase and upon DNA damage. ATR (ATM and Rad3-related) kinase mediates DNA damage-response of condensin-mediated genome organization. Our study describes a function of H3K56 acetylation that neutralizes condensin-mediated genome organization.