Abstract
Recent advances in our understanding of the three-dimensional organization of the eukaryotic nucleus have rendered the spatial distribution of genes increasingly relevant. In a recent work (Tsochatzidou et al., Nucleic Acids Res 45:5818–5828, 2017), we proposed the existence of a functional compartmentalization of the yeast genome according to which, genes occupying the chromosomal regions at the nuclear periphery have distinct structural, functional and evolutionary characteristics compared to their centromeric–proximal counterparts. Around the same time, it was also shown that the genome of Saccharomyces cerevisiae is organized in topologically associated domains (TADs), which are largely associated with the replication timing. In this work, we proceed to investigate whether such units of three-dimensional genomic organization can be linked to transcriptional activity as a driving force for the shaping of genomic architecture. Through the application of a simple boundary-calling criterion in genome-wide 3C data, we define ~100 TAD-like domains which can be clustered in six different classes with radically different nucleosomal organizations, significant variations in transcription factor binding and uneven chromosomal distribution. Approximately ~20% of the genome is found to be confined in regions with “closed” chromatin structure around gene promoters. Most interestingly, we find both “open” and “closed” regions to be segregated, in the sense that they tend to avoid inter-chromosomal interactions. Our data further enforce the notion of a marked compartmentalization of the yeast genome in isolated territories, with implications in its function and evolution.
Similar content being viewed by others
References
Adamczyk J, Deregowska A, Panek A et al (2016) Affected chromosome homeostasis and genomic instability of clonal yeast cultures. Curr Genet 62:405–418. doi:10.1007/s00294-015-0537-3
Babu MM, Janga SC, de Santiago I, Pombo A (2008) Eukaryotic gene regulation in three dimensions and its impact on genome evolution. Curr Opin Genet Dev 18:571–582. doi:10.1016/j.gde.2008.10.002
Bickmore WA, van Steensel B (2013) Genome architecture: domain organization of interphase chromosomes. Cell 152:1270–1284. doi:10.1016/j.cell.2013.02.001
Bonev B, Cavalli G (2016) Organization and function of the 3D genome. Nat Rev Genet 17:661–678. doi:10.1038/nrg.2016.112
Brackley CA, Brown JM, Waithe D et al (2016) Predicting the three-dimensional folding of cis-regulatory regions in mammalian genomes using bioinformatic data and polymer models. Genome Biol 17:1–16. doi:10.1186/s13059-016-0909-0
Caron H, van Schaik B, van der Mee M et al (2001) The human transcriptome map: clustering of highly expressed genes in chromosomal domains. Science 291:1289–1292. doi:10.1126/science.1056794
Cook PR (2010) A model for all genomes: the role of transcription factories. J Mol Biol 395:1–10. doi:10.1016/j.jmb.2009.10.031
Corrales Berjano M, Rosadfo A, Cortini R et al (2017) Clustering of Drosophila housekeeping promoters facilitates their expression. Genome Res 27:1153–1161
Crane E, Bian Q, McCord RP et al (2015) Condensin-driven remodelling of X chromosome topology during dosage compensation. Nature 523:240–244. doi:10.1038/nature14450
de Boer CG, Hughes TR (2012) YeTFaSCo: a database of evaluated yeast transcription factor sequence specificities. Nucleic Acids Res 40:D169–D179. doi:10.1093/nar/gkr993
Du M, Bai L (2017) 3D clustering of co-regulated genes and its effect on gene expression. Curr Genet. doi:10.1007/s00294-017-0712-9
Duan Z, Andronescu M, Schutz K et al (2010) A three-dimensional model of the yeast genome. Nature 465:363–367. doi:10.1038/nature08973
Elgin SCR, Reuter G (2013) Position-effect variegation, heterochromatin formation, and gene silencing in Drosophila. Cold Spring Harb Perspect Biol 5:a017780. doi:10.1101/cshperspect.a017780
Eser U, Chandler-Brown D, Ay F et al (2017) Form and function of topologically associating genomic domains in budding yeast. Proc Natl Acad Sci USA 114:E3061–E3070. doi:10.1073/pnas.1612256114
Gibcus JH, Dekker J (2013) The hierarchy of the 3D genome. Mol Cell 49:773–782. doi:10.1016/j.molcel.2013.02.011
Gordân R, Murphy KF, McCord RP et al (2011) Curated collection of yeast transcription factor DNA binding specificity data reveals novel structural and gene regulatory insights. Genome Biol 12:R125. doi:10.1186/gb-2011-12-12-r125
Gottschling DE, Aparicio OM, Billington BL, Zakian VA (1990) Position effect at S. cerevisiae telomeres: reversible repression of Pol II transcription. Cell 63:751–762. doi:10.1016/0092-8674(90)90141-Z
Harbison CT, Gordon DB, Lee TI et al (2004) Transcriptional regulatory code of a eukaryotic genome. Nature 431:99–104. doi:10.1038/nature02800
Iwasaki O, Noma KI (2016) Condensin-mediated chromosome organization in fission yeast. Curr Genet 62:739–743
Janga SC, Collado-Vides J, Babu MM (2008) Transcriptional regulation constrains the organization of genes on eukaryotic chromosomes. Proc Natl Acad Sci USA 105:15761–15766. doi:10.1073/pnas.0806317105
Jenuwein T, Allis CD (2001) Translating the histone code. Science 293:1074–1080. doi:10.1126/science.1063127
Jiang C, Pugh BF (2009) A compiled and systematic reference map of nucleosome positions across the Saccharomyces cerevisiae genome. Genome Biol 10:R109
Lang GI, Murray AW (2011) Mutation rates across budding yeast chromosome VI are correlated with replication timing. Genome Biol Evol 3:799–811. doi:10.1093/gbe/evr054
Lee W, Tillo D, Bray N et al (2007) A high-resolution atlas of nucleosome occupancy in yeast. Nat Genet 39:1235–1244. doi:10.1038/ng2117
Lercher MJ, Urrutia AO, Hurst LD (2002) Clustering of housekeeping genes provides a unified model of gene order in the human genome. Nat Genet 31:180–183. doi:10.1038/ng887
Lieberman-Aiden E, van Berkum NL, Williams L et al (2009) Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326:289–293. doi:10.1126/science.1181369
Marenduzzo D, Micheletti C, Cook PR (2006) Entropy-driven genome organization. Biophys J 90:3712–3721. doi:10.1529/biophysj.105.077685
Mavrich TN, Ioshikhes IP, Venters BJ et al (2008) A barrier nucleosome model for statistical positioning of nucleosomes throughout the yeast genome. Genome Res 18:1073–1083
Millar CB, Grunstein M (2006) Genome-wide patterns of histone modifications in yeast. Nat Rev Mol Cell Biol 7:657–666. doi:10.1038/nrm1986
Nikolaou C, Althammer S, Beato M, Guigó R (2010) Structural constraints revealed in consistent nucleosome positions in the genome of S. cerevisiae. Epigenet Chromatin 3:20
Nikolaou C, Bermúdez I, Manichanh C et al (2013) Topoisomerase II regulates yeast genes with singular chromatin architectures. Nucleic Acids Res 41:9243–9256. doi:10.1093/nar/gkt707
Pope BD, Ryba T, Dileep V et al (2014) Topologically associating domains are stable units of replication-timing regulation. Nature 515:402–405. doi:10.1038/nature13986
Reimand J, Kull M, Peterson H et al (2007) G:profiler-a web-based toolset for functional profiling of gene lists from large-scale experiments. Nucleic Acids Res 35:W193–W200. doi:10.1093/nar/gkm226
Rhode PR, Elsasser S, Campbell JL (1992) Role of multifunctional autonomously replicating sequence binding factor 1 in the initiation of DNA replication and transcriptional control in Saccharomyces cerevisiae. Mol Cell Biol 12:1064–1077
Riddle NC, Minoda A, Kharchenko PV et al (2011) Plasticity in patterns of histone modifications and chromosomal proteins in Drosophila heterochromatin. Genome Res 21:147–163. doi:10.1101/gr.110098.110
Rosin D, Hornung G, Tirosh I et al (2012) Promoter nucleosome organization shapes the evolution of gene expression. PLoS Genet 8:e1002579. doi:10.1371/journal.pgen.1002579
Schelling TC (1971) Dynamic models of segregation. J Math Sociol 1:143–186
Shivaswamy S, Bhinge A, Zhao Y et al (2008) Dynamic remodeling of individual nucleosomes across a eukaryotic genome in response to transcriptional perturbation. PLoS Biol 6:e65. doi:10.1371/journal.pbio.0060065
Siepel A, Bejerano G, Pedersen JS et al (2005) Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res 15:1034–1050. doi:10.1101/gr.3715005
Tirosh I, Barkai N (2008) Two strategies for gene regulation by promoter nucleosomes. Genome Res 18:1084–1091. doi:10.1101/gr.076059.108
Tsochatzidou M, Malliarou M, Papanikolaou N et al (2017) Genome urbanization: clusters of topologically co-regulated genes delineate functional compartments in the genome of Saccharomyces cerevisiae. Nucleic Acids Res 45:5818–5828. doi:10.1093/nar/gkx198
Ulianov SV, Khrameeva EE, Gavrilov AA et al (2016) Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains. Genome Res 26:70–84. doi:10.1101/gr.196006.115
Vinogradov AE (2004) Compactness of human housekeeping genes: selection for economy or genomic design? Trends Genet 20:248–253
Warnecke T, Parmley JL, Hurst LD (2008) Finding exonic islands in a sea of non-coding sequence: splicing related constraints on protein composition and evolution are common in intron-rich genomes. Genome Biol 9:R29
Warnecke T, Becker E, Facciotti MT et al (2013) Conserved substitution patterns around nucleosome footprints in eukaryotes and Archaea derive from frequent nucleosome repositioning through evolution. PLoS Comput Biol 9:e1003373. doi:10.1371/journal.pcbi.1003373
Yuan G-C, Liu Y-J, Dion MF et al (2005) Genome-scale identification of nucleosome positions in S. cerevisiae. Science 309:626–630. doi:10.1126/science.1112178
Zirkel A, Papantonis A (2014) Transcription as a force partitioning the eukaryotic genome. Biol Chem 395:1301–1305. doi:10.1515/hsz-2014-0196
Acknowledgements
The author would like to thank Maria Malliarou and Antonios Klonizakis for discussions on the general aspects presented in this study.
Author information
Authors and Affiliations
Corresponding author
Additional information
Communicated by M. Kupiec.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Nikolaou, C. Invisible cities: segregated domains in the yeast genome with distinct structural and functional attributes. Curr Genet 64, 247–258 (2018). https://doi.org/10.1007/s00294-017-0731-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00294-017-0731-6