Layered on top of information conveyed by DNA sequence and chromatin are higher order structures that encompass portions of chromosomes, entire chromosomes, and even whole genomes1, 2, 3. Interphase chromosomes are not positioned randomly within the nucleus, but instead adopt preferred conformations4, 5, 6, 7. Disparate DNA elements co-localize into functionally defined aggregates or ‘factories’ for transcription8 and DNA replication9. In budding yeast, Drosophila and many other eukaryotes, chromosomes adopt a Rabl configuration, with arms extending from centromeres adjacent to the spindle pole body to telomeres that abut the nuclear envelope10, 11, 12. Nonetheless, the topologies and spatial relationships of chromosomes remain poorly understood. Here we developed a method to globally capture intra- and inter-chromosomal interactions, and applied it to generate a map at kilobase resolution of the haploid genome of Saccharomyces cerevisiae. The map recapitulates known features of genome organization, thereby validating the method, and identifies new features. Extensive regional and higher order folding of individual chromosomes is observed. Chromosome XII exhibits a striking conformation that implicates the nucleolus as a formidable barrier to interaction between DNA sequences at either end. Inter-chromosomal contacts are anchored by centromeres and include interactions among transfer RNA genes, among origins of early DNA replication and among sites where chromosomal breakpoints occur. Finally, we constructed a three-dimensional model of the yeast genome. Our findings provide a glimpse of the interface between the form and function of a eukaryotic genome.
At a glance
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- Supplementary Information (11M)
This file contains Supplementary Results, Methods, Data Analysis, References and Validation of Methods, Supplementary Tables 1- 4 and 14 -15 (for Supplementary Tables 5-13 see separate excel files) and Supplementary Figures 1-18 with legends. Minor errors in this file were corrected on 19 May 2010.
- Supplementary Table 5 (6.6M)
This file contains a list of intra-chromosomal interactions identified from HindIII libraries at the threshold of FDR 1%.
- Supplementary Table 6 (22.7M)
This file contains a list of inter-chromosomal interactions identified from HindIII libraries at the threshold of FDR 1%.
- Supplementary Table 7 (3M)
This file contains a list of intra-chromosomal interactions identified from EcoRI libraries at the threshold of FDR 1%.
- Supplementary Table 8 (6.7M)
This file contains a list of inter-chromosomal interactions identified from EcoRI libraries at the threshold of FDR 1%.
- Supplementary Table 9 (27K)
This file contains the statistical data with respect to intra- and inter-chromosomal interactions-HindIII.
- Supplementary Table 10 (54K)
This file contains a list of intra-chromosomal interactions between the 20 and 30 kb regions of the ends of the chromosomes.
- Supplementary Table 11 (146K)
This file contains a list of Inter-chromosomal telomere pairing.
- Supplementary Table 12 (27K)
This file contains a list of primers used in this project.
- Supplementary Table 13 (392K)
This file contains a list of mappable HindIII and EcoRI fragments in each chromosome.