The 3D Organization of the Yeast Genome Correlates with Co-Expression and Reflects Functional Relations between Genes

The spatial organization of eukaryotic genomes is thought to play an important role in regulating gene expression. The recent advances in experimental methods including chromatin capture techniques, as well as the large amounts of accumulated gene expression data allow studying the relationship between spatial organization of the genome and co-expression of protein-coding genes. To analyse this genome-wide relationship at a single gene resolution, we combined the interchromosomal DNA contacts in the yeast genome measured by Duan et al. with a comprehensive collection of 1,496 gene expression datasets. We find significant enhancement of co-expression among genes with contact links. The co-expression is most prominent when two gene loci fall within 1,000 base pairs from the observed contact. We also demonstrate an enrichment of inter-chromosomal links between functionally related genes, which suggests that the non random nature of the genome organization serves to facilitate coordinated transcription in groups of genes.

[1]  Andrzej Kudlicki,et al.  High-resolution timing of cell cycle-regulated gene expression , 2007, Proceedings of the National Academy of Sciences.

[2]  L. Mirny,et al.  Iterative Correction of Hi-C Data Reveals Hallmarks of Chromosome Organization , 2012, Nature Methods.

[3]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

[4]  Christophe Zimmer,et al.  Principles of chromosomal organization: lessons from yeast , 2011, The Journal of cell biology.

[5]  Reza Kalhor,et al.  Genome architectures revealed by tethered chromosome conformation capture and population-based modeling , 2011, Nature Biotechnology.

[6]  J. Haber,et al.  Lack of chromosome territoriality in yeast: promiscuous rejoining of broken chromosome ends. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[7]  K. Sandhu,et al.  Circular chromosome conformation capture (4C) uncovers extensive networks of epigenetically regulated intra- and interchromosomal interactions , 2006, Nature Genetics.

[8]  M. McQueen,et al.  The Meaning of the Gene , 2000, Heredity.

[9]  J. Fuchs,et al.  Centromere clustering is a major determinant of yeast interphase nuclear organization. , 2000, Journal of cell science.

[10]  D. Botstein,et al.  Genomic expression programs in the response of yeast cells to environmental changes. , 2000, Molecular biology of the cell.

[11]  O. Gadal,et al.  Genome organization and function: a view from yeast and Arabidopsis. , 2010, Molecular plant.

[12]  M. Babu,et al.  Eukaryotic gene regulation in three dimensions and its impact on genome evolution. , 2008, Current opinion in genetics & development.

[13]  Jean-Christophe Olivo-Marin,et al.  High-resolution statistical mapping reveals gene territories in live yeast , 2008, Nature Methods.

[14]  Tom Misteli,et al.  Cell biology: Chromosome territories , 2007, Nature.

[15]  Yuanfang Guan,et al.  Functional Analysis of Gene Duplications in Saccharomyces cerevisiae , 2007, Genetics.

[16]  R. Sternglanz,et al.  Perinuclear localization of chromatin facilitates transcriptional silencing , 1998, Nature.

[17]  Hideki Tanizawa,et al.  Mapping of long-range associations throughout the fission yeast genome reveals global genome organization linked to transcriptional regulation , 2010, Nucleic acids research.

[18]  Tom Misteli,et al.  Spatial Positioning A New Dimension in Genome Function , 2004, Cell.

[19]  A. Tanay,et al.  Probabilistic modeling of Hi-C contact maps eliminates systematic biases to characterize global chromosomal architecture , 2011, Nature Genetics.

[20]  Job Dekker,et al.  The three 'C' s of chromosome conformation capture: controls, controls, controls , 2005, Nature Methods.

[21]  W Ansorge,et al.  The nucleotide sequence of Saccharomyces cerevisiae chromosome XVI. , 1997, Nature.

[22]  David Botstein,et al.  The nucleotide sequence of yeast chromosome XVI , 1997 .

[23]  Tom Misteli,et al.  The Meaning of Gene Positioning , 2008, Cell.

[24]  Cameron S. Osborne,et al.  Active genes dynamically colocalize to shared sites of ongoing transcription , 2004, Nature Genetics.

[25]  B. Dujon,et al.  The nucleotide sequence of Saccharomyces cerevisiae chromosome VII. , 1997, Nature.

[26]  F. Alber,et al.  Physical tethering and volume exclusion determine higher-order genome organization in budding yeast , 2012, Genome research.

[27]  Romain Koszul,et al.  Normalization of a chromosomal contact map , 2012, BMC Genomics.

[28]  Masaki Sasai,et al.  Dynamical modeling of three-dimensional genome organization in interphase budding yeast. , 2012, Biophysical journal.

[29]  Patrick Heun,et al.  MAP kinase signaling induces nuclear reorganization in budding yeast , 2000, Current Biology.

[30]  K. H. Wolfe,et al.  Molecular evidence for an ancient duplication of the entire yeast genome , 1997, Nature.

[31]  Pamela A. Silver,et al.  Genome-Wide Localization of the Nuclear Transport Machinery Couples Transcriptional Status and Nuclear Organization , 2004, Cell.

[32]  Prabhakar R. Gudla,et al.  Allele-specific nuclear positioning of the monoallelically expressed astrocyte marker GFAP. , 2008, Genes & development.

[33]  B. Steensel,et al.  Nuclear organization of active and inactive chromatin domains uncovered by chromosome conformation capture–on-chip (4C) , 2006, Nature Genetics.

[34]  B. Jones,et al.  Global identification of yeast chromosome interactions using Genome conformation capture. , 2009, Fungal genetics and biology : FG & B.

[35]  Michael Ruogu Zhang,et al.  Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. , 1998, Molecular biology of the cell.

[36]  Christophe Zimmer,et al.  A Predictive Computational Model of the Dynamic 3D Interphase Yeast Nucleus , 2012, Current Biology.

[37]  I. Amit,et al.  Comprehensive mapping of long range interactions reveals folding principles of the human genome , 2011 .

[38]  S. Gasser,et al.  The budding yeast nucleus. , 2010, Cold Spring Harbor perspectives in biology.

[39]  Alex E. Lash,et al.  Gene Expression Omnibus: NCBI gene expression and hybridization array data repository , 2002, Nucleic Acids Res..

[40]  P. Fraser,et al.  Nuclear organization of the genome and the potential for gene regulation , 2007, Nature.

[41]  J. Dekker,et al.  Capturing Chromosome Conformation , 2002, Science.

[42]  J. Collado-Vides,et al.  Transcriptional regulation constrains the organization of genes on eukaryotic chromosomes , 2008, Proceedings of the National Academy of Sciences.

[43]  William Stafford Noble,et al.  A Three-Dimensional Model of the Yeast Genome , 2010, Nature.

[44]  E. van Nimwegen,et al.  The functional importance of telomere clustering: global changes in gene expression result from SIR factor dispersion. , 2009, Genome research.

[45]  J. O'Sullivan Yeast chromosomal interactions and nuclear architecture. , 2010, Current opinion in cell biology.

[46]  Gerd Gruenert,et al.  Chromosome positioning and the clustering of functionally related loci in yeast is driven by chromosomal interactions , 2012, Nucleus.

[47]  H. Scherthan,et al.  The clustering of telomeres and colocalization with Rap1, Sir3, and Sir4 proteins in wild-type Saccharomyces cerevisiae , 1996, The Journal of cell biology.