Abstract
The genetic information is stored in the eukaryotic nucleus in the form of chromatin. This is a macromolecular entity that includes genomic DNA and histone proteins that form nucleosomes, plus a large variety of chromatin-associated non-histone proteins. Chromatin is structurally and functionally organised at various levels. One reveals the linear topography of DNA, histones and their post-translational modifications and non-histone proteins along each chromosome. This level provides regulatory information about the association of genomic elements with particular signatures that have been used to define chromatin states. Importantly, these chromatin states correlate with structural and functional genomic features. Another regulatory layer is established at the level of the 3D organisation of chromatin within the nucleus, which has been revealed clearly as non-random. Instead, a variety of intra- and inter-chromosomal genomic domains with specific epigenetic and functional properties has been identified. In this review, we discuss how the recent advances in genomic approaches have contributed to our understanding of these two levels of genome architecture. We have emphasised our analysis with the aim of integrating information available for yeast, Arabidopsis, Drosophila, and mammalian cells. We consider that this comparative study helps define common and unique features in each system, providing a basis to better understand the complexity of genome organisation.
Similar content being viewed by others
References
Bannister AJ, Kouzarides T (2011) Regulation of chromatin by histone modifications. Cell Res 21:381–395. doi:10.1038/cr.2011.22
Bantignies F et al (2011) Polycomb-dependent regulatory contacts between distant Hox loci in Drosophila. Cell 144:214–226. doi:10.1016/j.cell.2010.12.026
Barski A et al (2007) High-resolution profiling of histone methylations in the human genome. Cell 129:823–837. doi:10.1016/j.cell.2007.05.009
Belmont AS (2014) Large-scale chromatin organization: the good, the surprising, and the still perplexing. Curr Opin Cell Biol 26:69–78. doi:10.1016/j.ceb.2013.10.002
Berger AB et al (2008) High-resolution statistical mapping reveals gene territories in live yeast. Nat Methods 5:1031–1037. doi:10.1038/nmeth.1266
Bernatavichute YV, Zhang X, Cokus S, Pellegrini M, Jacobsen SE (2008) Genome-wide association of histone H3 lysine nine methylation with CHG DNA methylation in Arabidopsis thaliana. PLoS One 3:e3156. doi:10.1371/journal.pone.0003156
Biesinger J, Wang Y, Xie X (2013) Discovering and mapping chromatin states using a tree hidden Markov model. BMC Bioinformatics 14(Suppl 5):S4. doi:10.1186/1471-2105-14-S5-S4
Brown EJ, Bachtrog D (2014) The chromatin landscape of Drosophila: comparisons between species, sexes, and chromosomes. Genome Res 24:1125–1137. doi:10.1101/gr.172155.114
Calo E, Wysocka J (2013) Modification of enhancer chromatin: what, how, and why? Mol Cell 49:825–837. doi:10.1016/j.molcel.2013.01.038
Cheutin T, Cavalli G (2014) Polycomb silencing: from linear chromatin domains to 3D chromosome folding. Curr Opin Genetics Dev 25:30–37. doi:10.1016/j.gde.2013.11.016
Christophorou MA et al (2014) Citrullination regulates pluripotency and histone H1 binding to chromatin. Nature 507:104–108. doi:10.1038/nature12942
Crevillén P, Sonmez C, Wu Z, Dean C (2012) A gene loop containing the floral repressor FLC is disrupted in the early phase of vernalization. EMBO J 32:140–148. doi:10.1038/emboj.2012.324
Czermin B, Schotta G, Hülsmann BB, Brehm A, Becker PB, Reuter G, Imhof A (2001) Physical and functional association of SU(VAR)3-9 and HDAC1 in Drosophila. EMBO Rep 2:915–919. doi:10.1093/embo-reports/kve210
de Wit E, de Laat W (2012) A decade of 3C technologies: insights into nuclear organization. Genes Dev 26:11–24. doi:10.1101/gad.179804.111
Dekker J, Rippe K, Dekker M, Kleckner N (2002) Capturing chromosome conformation. Science 295:1306–1311. doi:10.1126/science.1067799
Dekker J, Marti-Renom MA, Mirny LA (2013) Exploring the three-dimensional organization of genomes: interpreting chromatin interaction data. Nature Rev Genet 14:390–403. doi:10.1038/nrg3454
DeMare LE, Leng J, Cotney J, Reilly SK, Yin J, Sarro R, Noonan JP (2013) The genomic landscape of cohesin-associated chromatin interactions. Genome Res 23:1224–1234. doi:10.1101/gr.156570.113
Dixon JR et al (2012) Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485:376–380. doi:10.1038/nature11082
Dostie J et al (2006) Chromosome conformation capture carbon copy (5C): a massively parallel solution for mapping interactions between genomic elements. Genome Res 16:1299–1309. doi:10.1101/gr.5571506
Dowen JM et al (2014) Control of cell identity genes occurs in insulated neighborhoods in mammalian chromosomes. Cell 159:374–387. doi:10.1016/j.cell.2014.09.030
Duan Z et al (2010) A three-dimensional model of the yeast genome. Nature 465:363–367. doi:10.1038/nature08973
Ernst J, Kellis M (2010) Discovery and characterization of chromatin states for systematic annotation of the human genome. Nat Biotechnol 28:817–825. doi:10.1038/nbt.1662
Ernst J, Kellis M (2012) ChromHMM: automating chromatin-state discovery and characterization. Nat Methods 9:215–216. doi:10.1038/nmeth.1906
Ernst J, Kellis M (2013) Interplay between chromatin state, regulator binding, and regulatory motifs in six human cell types. Genome Res 23:1142–1154. doi:10.1101/gr.144840.112
Ernst J et al (2011) Mapping and analysis of chromatin state dynamics in nine human cell types. Nature 473:43–49. doi:10.1038/nature09906
Feng S, Jacobsen SE (2011) Epigenetic modifications in plants: an evolutionary perspective. Curr Opin Plant Biol 14:179–186. doi:10.1016/j.pbi.2010.12.002
Feng S, Cokus SJ, Schubert V, Zhai J, Pellegrini M, Jacobsen SE (2014) Genome-wide Hi-C analyses in wild-type and mutants reveal high-resolution chromatin interactions in Arabidopsis. Mol Cell 55:694–707. doi:10.1016/j.molcel.2014.07.008
Filion GJ et al (2010) Systematic protein location mapping reveals five principal chromatin types in Drosophila cells. Cell 143:212–224. doi:10.1016/j.cell.2010.09.009
Fischer A, Hofmann I, Naumann K, Reuter G (2006) Heterochromatin proteins and the control of heterochromatic gene silencing in Arabidopsis. J Plant Physiol 163:358–368. doi:10.1016/j.jplph.2005.10.015
Fullwood MJ et al (2009) An oestrogen-receptor-alpha-bound human chromatin interactome. Nature 462:58–64. doi:10.1038/nature08497
Grob S, Schmid MW, Luedtke NW, Wicker T, Grossniklaus U (2013) Characterization of chromosomal architecture in Arabidopsis by chromosome conformation capture. Genome Biol 14:R129. doi:10.1186/gb-2013-14-11-r129
Grob S, Schmid MW, Grossniklaus U (2014) Hi-C analysis in Arabidopsis identifies the KNOT, a structure with similarities to the flamenco locus of Drosophila. Mol Cell 55:678–693. doi:10.1016/j.molcel.2014.07.009
Gu SG, Fire A (2010) Partitioning the C. elegans genome by nucleosome modification, occupancy, and positioning. Chromosoma 119:73–87. doi:10.1007/s00412-009-0235-3
Guelen L et al (2008) Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions. Nature 453:948–951. doi:10.1038/nature06947
Gurard-Levin ZA, Almouzni G (2014) Histone modifications and a choice of variant: a language that helps the genome express itself. F1000Prime Rep 6:76 doi:10.12703/P6-76
Hagège H et al (2007) Quantitative analysis of chromosome conformation capture assays (3C-qPCR). Nat Protoc 2:1722–1733. doi:10.1038/nprot.2007.243
Handoko L et al (2011) CTCF-mediated functional chromatin interactome in pluripotent cells. Nat Genet 43:630–638. doi:10.1038/ng.857
Happel N, Doenecke D (2009) Histone H1 and its isoforms: contribution to chromatin structure and function. Gene 431:1–12
Heitz E (1928) Das Heterochromatin der Moose. Jahrb Wiss Botanik 69:762–818
Henikoff S, Shilatifard A (2011) Histone modification: cause or cog? Trends Genet 27:389–396. doi:10.1016/j.tig.2011.06.006
Ho JWK et al (2014) Comparative analysis of metazoan chromatin organization. Nature 512:449–452. doi:10.1038/nature13415
Hon G, Ren B, Wang W (2008) ChromaSig: a probabilistic approach to finding common chromatin signatures in the human genome. PLoS Computat Biol 4:e1000201. doi:10.1371/journal.pcbi.1000201
Horike S-i, Cai S, Miyano M, Cheng J-F, Kohwi-Shigematsu T (2005) Loss of silent-chromatin looping and impaired imprinting of DLX5 in Rett syndrome. Nature Genet 37:31–40. doi:10.1038/ng1491
Johnson L, Cao X, Jacobsen S (2002) Interplay between two epigenetic marks. DNA methylation and histone H3 lysine 9 methylation. Curr Biol 12:1360–1367
Kharchenko PV et al (2010) Comprehensive analysis of the chromatin landscape in Drosophila melanogaster. Nature 471:480–485. doi:10.1038/nature09725
Kouzarides T (2007) Chromatin modifications and their function. Cell 128:693–705. doi:10.1016/j.cell.2007.02.005
Larson JL, Yuan G-C (2010) Epigenetic domains found in mouse embryonic stem cells via a hidden Markov model. BMC Bioinformatics 11:557. doi:10.1186/1471-2105-11-557
Li G et al (2012) Extensive promoter-centered chromatin interactions provide a topological basis for transcription regulation. Cell 148:84–98. doi:10.1016/j.cell.2011.12.014
Lieberman-Aiden E 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
Liu CL, Kaplan T, Kim M, Buratowski S, Schreiber SL (2005) PLOS Biology: single-nucleosome mapping of histone modifications in S. cerevisiae. PLoS Biol 3:e328. doi:10.1371/journal.pbio.0030328
Liu T et al (2011) Broad chromosomal domains of histone modification patterns in C. elegans. Genome Res 21:227–236
Loomis RJ et al (2009) Chromatin binding of SRp20 and ASF/SF2 and dissociation from mitotic chromosomes is modulated by histone H3 serine 10 phosphorylation. Mol Cell 33:450–461. doi:10.1016/j.molcel.2009.02.003
Louwers M, Splinter E, van Driel R, de Laat W, Stam M (2009) Studying physical chromatin interactions in plants using chromosome conformation capture (3C). Nat Protoc 4:1216–1229. doi:10.1038/nprot.2009.113
Maze I, Noh K-M, Soshnev AA, Allis CD (2014) Every amino acid matters: essential contributions of histone variants to mammalian development and disease. Nature Rev Genet 15:259–271. doi:10.1038/nrg3673
McDaniell R et al (2010) Heritable individual-specific and allele-specific chromatin signatures in humans. Science 328:235–239. doi:10.1126/science.1184655
Mikkelsen TS et al (2007) Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448:553–560. doi:10.1038/nature06008
Moissiard G et al (2012) MORC family ATPases required for heterochromatin condensation and gene silencing. Science 336:1448–1451. doi:10.1126/science.1221472
Nagano T et al (2013) Single-cell Hi-C reveals cell-to-cell variability in chromosome structure. Nature 502:59–64. doi:10.1038/nature12593
Nora EP et al (2012) Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature 485:381–385. doi:10.1038/nature11049
Ott RW, Chua NH (1990) Enhancer sequences from Arabidopsis thaliana obtained by library transformation of Nicotiana tabacum. Mol Gen Genet 223:169–179
Piacentini L, Fanti L, Negri R, Del Vescovo V, Fatica A, Altieri F, Pimpinelli S (2009) Heterochromatin protein 1 (HP1a) positively regulates euchromatic gene expression through RNA transcript association and interaction with hnRNPs in Drosophila. PLoS Genet 5:e1000670. doi:10.1371/journal.pgen.1000670
Pombo A, Dillon N (2015) Three-dimensional genome architecture: players and mechanisms. Nat Rev Mol Cell Biol 16:245–257. doi:10.1038/nrm3965
Pope BD, Gilbert DM (2013) The replication domain model: regulating replicon firing in the context of large-scale chromosome architecture. J Mol Biol 425:4690–4695. doi:10.1016/j.jmb.2013.04.014
Rao SSP et al (2014) A 3d map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159:1665–1680. doi:10.1016/j.cell.2014.11.021
Riddle NC 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
RoadmapEpigenomicsConsortium et al (2015) Integrative analysis of 111 reference human epigenomes. Nature 518:317–330. doi:10.1038/nature14248
Roudier F et al (2011) Integrative epigenomic mapping defines four main chromatin states in Arabidopsis. EMBO J 30:1928–1938. doi:10.1038/emboj.2011.103
Ryba T et al (2010) Evolutionarily conserved replication timing profiles predict long-range chromatin interactions and distinguish closely related cell types. Genome Res 20:761–770. doi:10.1101/gr.099655.109
Saint-Andre V, Batsche E, Rachez C, Muchardt C (2011) Histone H3 lysine 9 trimethylation and HP1gamma favor inclusion of alternative exons. Nat Struct Mol Biol 18:337–344. doi:10.1038/nsmb.1995
Sanyal A, Lajoie BR, Jain G, Dekker J (2012) The long-range interaction landscape of gene promoters. Nature 489:109–113. doi:10.1038/nature11279
Sequeira-Mendes J et al (2014) The functional topography of the Arabidopsis genome is organized in a reduced number of linear motifs of chromatin states. Plant Cell 26:2351–2366. doi:10.1105/tpc.114.124578
Sexton T et al (2012) Three-dimensional folding and functional organization principles of the Drosophila genome. Cell 148:458–472. doi:10.1016/j.cell.2012.01.010
Shu H, Wildhaber T, Siretskiy A, Gruissem W, Hennig L (2012) Distinct modes of DNA accessibility in plant chromatin. Nat Commun 3:1281. doi:10.1038/ncomms2259
Shu H et al (2014) Arabidopsis replacement histone variant H3.3 occupies promoters of regulated genes. Genome Biol 15:R62. doi:10.1186/gb-2014-15-4-r62
Simonis M et al (2006) Nuclear organization of active and inactive chromatin domains uncovered by chromosome conformation capture-on-chip (4C). Nature Genet 38:1348–1354. doi:10.1038/ng1896
Smemo S et al (2014) Obesity-associated variants within FTO form long-range functional connections with IRX3. Nature 507:371–375. doi:10.1038/nature13138
Spitz F, Furlong EEM (2012) Transcription factors: from enhancer binding to developmental control. Nature Rev Genet 13:613–626. doi:10.1038/nrg3207
Splinter E et al (2006) CTCF mediates long-range chromatin looping and local histone modification in the beta-globin locus. Genes Dev 20:2349–2354. doi:10.1101/gad.399506
Splinter E et al (2011) The inactive X chromosome adopts a unique three-dimensional conformation that is dependent on Xist RNA. Genes Dev 25:1371–1383. doi:10.1101/gad.633311
Stroud H, Otero S, Desvoyes B, Ramirez-Parra E, Jacobsen SE, Gutierrez C (2012) Genome-wide analysis of histone H3.1 and H3.3 variants in Arabidopsis thaliana. Proc Natl Acad Sci U S A 109:5370–5375. doi:10.1073/pnas.1203145109
Sundaresan V et al (1995) Patterns of gene action in plant development revealed by enhancer trap and gene trap transposable elements. Genes Dev 9:1797–1810
Tark-Dame M, Jerabek H, Manders EM, Heermann DW, van Driel R (2014) Depletion of the chromatin looping proteins CTCF and cohesin causes chromatin compaction: insight into chromatin folding by polymer modelling. PLoS Comput Biol 10:e1003877. doi:10.1371/journal.pcbi.1003877
Tolhuis B et al (2011) Interactions among Polycomb domains are guided by chromosome architecture. PLoS Genet 7:e1001343. doi:10.1371/journal.pgen.1001343
Visel A et al (2009) ChIP-seq accurately predicts tissue-specific activity of enhancers. Nature 457:854–858. doi:10.1038/nature07730
Wang C et al (2014) Genome-wide analysis of local chromatin packing in Arabidopsis thaliana. Genome Res. doi:10.1101/gr.170332.113
Williamson I et al (2014) Spatial genome organization: contrasting views from chromosome conformation capture and fluorescence in situ hybridization. Genes Dev 28:2778–2791. doi:10.1101/gad.251694.114
Wollmann H, Holec S, Alden K, Clarke ND, Jacques P-É, Berger F (2012) Dynamic deposition of histone variant H3.3 accompanies developmental remodeling of the Arabidopsis transcriptome. PLoS Genet 8:e1002658. doi:10.1371/journal.pgen.1002658
Zhang Y et al (2012) Spatial organization of the mouse genome and its role in recurrent chromosomal translocations. Cell 148:908–921. doi:10.1016/j.cell.2012.02.002
Zhao Z et al (2006) Circular chromosome conformation capture (4C) uncovers extensive networks of epigenetically regulated intra- and interchromosomal interactions. Nature Genet 38:1341–1347. doi:10.1038/ng1891
Zhou J, Wang X, He K, Charron J-BF, Elling AA, Deng XW (2010) Genome-wide profiling of histone H3 lysine 9 acetylation and dimethylation in Arabidopsis reveals correlation between multiple histone marks and gene expression. Plant Mol Biol 72:585–595. doi:10.1007/s11103-009-9594-7
Zuin J et al (2014) Cohesin and CTCF differentially affect chromatin architecture and gene expression in human cells. Proc Natl Acad Sci U S A 111:996–1001. doi:10.1073/pnas.1317788111
Acknowledgments
We deeply thank all C.G. laboratory members for the insightful discussions and B. Desvoyes for the help with Fig. 2. Research at C.G. lab is supported by Ministerio de Economía y Competitividad (grant BFU2012–34821) and an institutional grant of Fundación Ramón Areces to the Centro de Biología Molecular Severo Ochoa.
Compliance with ethical standards
This is a review article that does not provide original data and is not a research involving human and/or animals. Informed consent is not applicable.
Conflict of interest
The authors declare that they have no competing interests.
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Sequeira-Mendes, J., Gutierrez, C. Genome architecture: from linear organisation of chromatin to the 3D assembly in the nucleus. Chromosoma 125, 455–469 (2016). https://doi.org/10.1007/s00412-015-0538-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00412-015-0538-5