Letter | Published:

A three-dimensional model of the yeast genome

Nature volume 465, pages 363367 (20 May 2010) | Download Citation

Abstract

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.

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Accessions

Data deposits

Sequencing data have been deposited in the Sequence Read Archive under accession number SRP002120. An interactive website for yeast chromosomal interactions can be found at http://noble.gs.washington.edu/proj/yeast-architecture.

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Acknowledgements

We appreciate the advice and assistance of M. Dorschner, the comments of S. Di Rienzi, B. Brewer and B. Byers, and the assistance of L. Zhang and G. Schroth (Illumina Inc.) in performing sequencing. We thank A. Brown for help with the 3D model. Supported by NIH grants P01GM081619, P41RR0011823, a post-doctoral fellowship (to M.A.) from the Natural Sciences and Engineering Research Council of Canada, and the Howard Hughes Medical Institute.

Author information

Author notes

    • Zhijun Duan
    •  & Mirela Andronescu

    These authors contributed equally to this work.

Affiliations

  1. Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98195-8056, USA

    • Zhijun Duan
    • , Yoo Jung Kim
    •  & C. Anthony Blau
  2. Department of Medicine, University of Washington Seattle, Washington 98195-8056, USA

    • Zhijun Duan
    • , Yoo Jung Kim
    • , Stanley Fields
    •  & C. Anthony Blau
  3. Department of Genome Sciences, University of Washington, Seattle, Washington 98195-5065, USA

    • Mirela Andronescu
    • , Sean McIlwain
    • , Choli Lee
    • , Jay Shendure
    • , Stanley Fields
    • , C. Anthony Blau
    •  & William S. Noble
  4. Graduate Program in Molecular and Cellular Biology, University of Washington, Seattle, Washington 98195-5065, USA

    • Kevin Schutz
  5. Howard Hughes Medical Institute

    • Stanley Fields

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Contributions

Z.D. devised the strategy for characterizing genome architecture, Z.D., J.S, S.F, C.A.B. and W.S.N. designed experiments, Z.D., K.S., Y.J.K., and C.L. performed experiments, Z.D., M.A., S.M., J.S., S.F., C.A.B. and W.S.N. analysed experimental data, M.A., K.S., J.S. and W.S.N. commented on the manuscript drafts, Z.D., S.F., and C.A.B. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to C. Anthony Blau or William S. Noble.

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    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.

Excel files

  1. 1.

    Supplementary Table 5

    This file contains a list of intra-chromosomal interactions identified from HindIII libraries at the threshold of FDR 1%.

  2. 2.

    Supplementary Table 6

    This file contains a list of inter-chromosomal interactions identified from HindIII libraries at the threshold of FDR 1%.

  3. 3.

    Supplementary Table 7

    This file contains a list of intra-chromosomal interactions identified from EcoRI libraries at the threshold of FDR 1%.

  4. 4.

    Supplementary Table 8

    This file contains a list of inter-chromosomal interactions identified from EcoRI libraries at the threshold of FDR 1%.

  5. 5.

    Supplementary Table 9

    This file contains the statistical data with respect to intra- and inter-chromosomal interactions-HindIII.

  6. 6.

    Supplementary Table 10

    This file contains a list of intra-chromosomal interactions between the 20 and 30 kb regions of the ends of the chromosomes.

  7. 7.

    Supplementary Table 11

    This file contains a list of Inter-chromosomal telomere pairing.

  8. 8.

    Supplementary Table 12

    This file contains a list of primers used in this project.

  9. 9.

    Supplementary Table 13

    This file contains a list of mappable HindIII and EcoRI fragments in each chromosome.

Protein data bank files

  1. 1.

    Supplementary Information

    This file contains a 3d model of the yeast genome. This file can be opened using Rasmol (http://rasmol.org/).

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DOI

https://doi.org/10.1038/nature08973

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