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The radial arrangement of the human chromosome 7 in the lymphocyte cell nucleus is associated with chromosomal band gene density

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Abstract

In the nuclei of human lymphocytes, chromosome territories are distributed according to the average gene density of each chromosome. However, chromosomes are very heterogeneous in size and base composition, and can contain both very gene-dense and very gene-poor regions. Thus, a precise analysis of chromosome organisation in the nuclei should consider also the distribution of DNA belonging to the chromosomal bands in each chromosome. To improve our understanding of the chromatin organisation, we localised chromosome 7 DNA regions, endowed with different gene densities, in the nuclei of human lymphocytes. Our results showed that this chromosome in cell nuclei is arranged radially with the gene-dense/GC-richest regions exposed towards the nuclear interior and the gene-poorest/GC-poorest ones located at the nuclear periphery. Moreover, we found that chromatin fibres from the 7p22.3 and the 7q22.1 bands are not confined to the territory of the bulk of this chromosome, protruding towards the inner part of the nucleus. Overall, our work demonstrates the radial arrangement of the territory of chromosome 7 in the lymphocyte nucleus and confirms that human genes occupy specific radial positions, presumably to enhance intra- and inter-chromosomal interaction among loci displaying a similar expression pattern, and/or similar replication timing.

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References

  • Andreozzi L, Federico C, Motta S, Saccone S, Sazanova AL, Sazanov AA, Smirnov AF, Galkina SA, Lukina NA, Rodionov AV, Carels N, Bernardi G (2001) Compositional mapping of chicken chromosomes and identification of the gene-richest regions. Chromosom Res 9:521–532

    Article  CAS  Google Scholar 

  • Andrulis ED, Neiman AM, Zappulla DC, Sternglanz R (1998) Perinuclear localization of chromatin facilitates transcriptional silencing. Nature 394:592–595

    Article  PubMed  CAS  Google Scholar 

  • Bernardi G (2004) Structural and evolutionary genomics. Natural selection in genome evolution. Elsevier, Amsterdam, The Netherlands

    Google Scholar 

  • Bickmore WA, van der Maarel SM (2003) Perturbations of chromatin structure in human genetic disease: recent advances. Hum Mol Genet 12:207–213

    Article  CAS  Google Scholar 

  • Boggs BA, Chinault AC (1997) Analysis of DNA replication by fluorescence in situ hybridization. Methods 13:259–270

    Article  PubMed  CAS  Google Scholar 

  • Bolzer A, Kreth G, Solovei I, Koehler D, Saracoglu K, Fauth C, Muller S, Eils R, Cremer C, Speicher MR, Cremer T (2005) Three-dimensional maps of all chromosomes in human male fibroblast nuclei and prometaphase rosettes. PLoS Biol 3(5):e157

    Article  PubMed  CAS  Google Scholar 

  • Boutanaev AM, Mikhaylova LM, Nurminsky DI (2005) The pattern of chromosome folding in interphase is outlined by the linear gene density profile. Mol Cell Biol 25:8379–8386

    Article  PubMed  CAS  Google Scholar 

  • Boyle S, Gilchrist S, Bridger JM, Mahy NL, Elis JA, Bickmore WA (2001) The spatial organization of human chromosome within the nuclei of normal and emerin-mutant cells. Hum Mol Genet 10:211–219

    Article  PubMed  CAS  Google Scholar 

  • Bridger JM, Boyle S, Kill IR, Bickmore WA (2000) Re-modelling of nuclear architecture in quiescent and senescent human fibroblasts. Curr Biol 10:149–152

    Article  PubMed  CAS  Google Scholar 

  • Brown KE, Guest SS, Smale ST, Hahm K, Merkenschlager M, Fisher AG (1997) Association of transcriptionally silent genes with ikaros complexes at centromeric heterochromatin. Cell 91:845–854

    Article  PubMed  CAS  Google Scholar 

  • Clemson CM, Hall LL, Byron M, McNeil J, Lawrence B (2006) The X chromosome is organized into a gene-rich outer rim and an internal core containing silenced nongenic sequences. Proc Natl Acad Sci USA 103:7688–7693

    Article  PubMed  CAS  Google Scholar 

  • Cockell M, Gasser SM (1999) Nuclear compartments and gene regulation. Curr Op Genet Dev 9:199–205

    Article  PubMed  CAS  Google Scholar 

  • Costantini M, Clay O, Federico C, Saccone S, Auletta F, Bernardi G (2007) Human chromosomal bands: nested structure, high definition map and molecular basis. Chromosoma 116:36–49

    Article  CAS  Google Scholar 

  • Cremer T, Cremer C (2001) Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nature Genet 2:292–301

    Article  CAS  Google Scholar 

  • Croft JA, Bridger JM, Boyle S, Perry P, Teague P, Bickmore WA (1999) Differences in the localization and morphology of chromosomes in the human nucleus. J Cell Biol 145:1119–1131

    Article  PubMed  CAS  Google Scholar 

  • D’Antoni S, Mattina T, Di Mare P, Federico C, Motta S, Saccone S (2004) Altered replication timing of the HIRA/Tuple1 locus in the DiGeorge and velocardiofacial syndromes. Gene 333:111–119

    Article  PubMed  CAS  Google Scholar 

  • D’Onofrio G, Ghosh TC, Saccone S (2007) Different functional classes of genes are characterized by different compositional properties. FEBS Lett 581:5819–5824

    Article  PubMed  CAS  Google Scholar 

  • Dutrillaux B, Couturier J, Richer C-L, Viegas-Pequinot E (1976) Sequence of DNA replication in 277 R- and Q-bands of human chromosomes using a BrdU treatment. Chromosoma 58:51–61

    Article  PubMed  CAS  Google Scholar 

  • Federico C, Saccone S, Bernardi G (1998) The gene-richest bands of human chromosomes replicate at the onset of the S-phase. Cytogenet Cell Genet 80:83–88

    Article  PubMed  CAS  Google Scholar 

  • Federico C, Andreozzi L, Saccone S, Bernardi G (2000) Gene density in the Giemsa bands of human chromosomes. Chromosom Res 8:737–746

    Article  CAS  Google Scholar 

  • Federico C, Saccone S, Andreozzi L, Motta S, Russo V, Carels N, Bernardi G (2004) The pig genome: compositional analysis and indentification of the gene-richest regions in chromosomes and nuclei. Gene 343:245–251

    Article  PubMed  CAS  Google Scholar 

  • Federico C, Cantarella CD, Scavo C, Saccone S, Bed’Hom B, Bernardi G (2005) Avian genomes: different karyotypes but a similar distribution of the GC-richest chromosome regions at interphase. Chromosom Res 13:785–793

    Article  CAS  Google Scholar 

  • Federico C, Scavo C, Cantarella CD, Motta S, Saccone S, Bernardi G (2006) Gene-rich and gene-poor chromosomal regions have different locations in the interphase nuclei of cold-blooded vertebrates. Chromosoma 115:123–128

    Article  PubMed  CAS  Google Scholar 

  • Ferreira J, Paolella G, Ramos C, Lamond AI (1997) Spatial organization of large-scale chromatin domains in the nucleus: a magnified view of single chromosome territories. Cell Biol 139:1597–1610

    Article  CAS  Google Scholar 

  • Foster HA, Bridger JM (2005) The genome and the nucleus: a marriage made by evolution. Genome organization and nuclear architecture. Chromosoma 114:212–229

    Article  PubMed  Google Scholar 

  • Francke U (1994) Digitized and differentially shaded human chromosome ideograms for genomic applications. Cytogenet Cell Genet 6:206–219

    Article  Google Scholar 

  • Furey TS, Haussler D (2003) Integration of the cytogenetic map with the draft human genome sequence. Hum Mol Genet 12:1037–1044

    Article  PubMed  CAS  Google Scholar 

  • Gilbert N, Boyle S, Fiegler H, Woodfine K, Carter NP, Bickmore WA (2004) Chromatin architecture of the human genome: gene-rich domains are enriched in open chromatin fibers. Cell 118:555–566

    Article  PubMed  CAS  Google Scholar 

  • IHGSC (International Human Genome Sequencing Consortium) (2004) Finishing the euchromatic sequence of the human genome. Nature 431:931–945

    Article  CAS  Google Scholar 

  • Kupper K, Kolbl A, Biener D, Dittrich S, von Hase J, Thormeyer T, Fiegler H, Carter NP, Speicher MR, Cremer T, Cremer M (2007) Radial chromatin positioning is shaped by local gene density, not by gene expression. Chromosoma 116:285–306

    Article  PubMed  Google Scholar 

  • Lukasova E, Kozubek S, Kozubek M, Falk M, Amrichova J (2002) The 3D structure of human chromosomes in cell nuclei. Chromosom Res 10:535–48

    Article  CAS  Google Scholar 

  • Masny PS, Bengtsson U, Chung S-A, Martin JH, van Engelen B, van der Maarel SM, Winokur ST (2004) Localization of 4q35.2 to the nuclear periphery: is FSHD a nuclear envelope disease? Hum Mol Genet 13:1857–1871

    Article  PubMed  CAS  Google Scholar 

  • Neusser M, Schubel V, Koch A, Cremer T, Müller S (2007) Evolutionary conserved, cell type and species-specific higher order chromatin arrangements in interphase nuclei of primates. Chromosoma 116:307–320

    Article  PubMed  Google Scholar 

  • Ono A, Kono K, Ikebe D, Muto A, Sun J, Kobayashi M, Ueda K, Melo JV, Igarashi K, Tashiro S (2007) Nuclear positioning of the BACH2 gene in BCR-ABL positive leukemic cells. Genes Chromosomes Cancer 46:67–74

    Article  PubMed  CAS  Google Scholar 

  • Petrova NV, Yarovaya OV, Razin SV (2006) Specific spatial organization of chromosomes in nuclei of primary human fibroblasts is maintained by nuclear matrix. Dokl Biochem Biophys 406:4–6

    Article  PubMed  CAS  Google Scholar 

  • Roix JJ, McQueen PG, Munson P, Parada LA, Misteli T (2003) Spatial proximity of traslocation-prone gene loci in human lymphomas. Nat. Genet 34:287–291

    Article  PubMed  CAS  Google Scholar 

  • Saccone S, De Sario A, Della Valle G, Bernardi G (1992) The highest gene concentrations in the human genome are in telomeric bands of metaphase chromosomes. Proc Natl Acad Sci USA 89:4913–4917

    Article  PubMed  CAS  Google Scholar 

  • Saccone S, Cacciò S, Perani P, Andreozzi L, Rapisarda A, Motta S, Bernardi G (1997) Compositional mapping of mouse chromosomes and identification of the gene-rich regions. Chromosom Res 5:293–300

    Article  CAS  Google Scholar 

  • Saccone S, Pavlicek A, Federico C, Paces J, Bernardi G (2001) Genes, isochores and bands in human chromosomes 21 and 22. Chromosom Res 9:533–539

    Article  CAS  Google Scholar 

  • Saccone S, Federico C, Bernardi G (2002) Localization of the gene-richest and the gene-poorest isochores in the interphase nuclei of mammals and birds. Gene 300:169–178

    Article  PubMed  CAS  Google Scholar 

  • Sadoni N, Langer S, Fauth C, Bernardi G, Cremer T, Turner BM, Zink D (1999) Nuclear organization of mammalian genomes: polar chromosome territories build up functionally distinct higher order compartments. J Cell Biol 146:1211–1226

    Article  PubMed  CAS  Google Scholar 

  • Scherer SW, Cheung J, MacDonald JR, Osborne LR, Nakabayashi K et al (2003) Human chromosome 7: DNA sequence and biology. Science 300:767–772

    Article  PubMed  CAS  Google Scholar 

  • Solovei I, Cavallo A, Schermelleh L, Jaunin F, Scasselati C, Cmarko D, Cremer C, Fakan S, Cremer T (2002) Spatial preservation of nuclear chromatin architecture during three-dimensional fluorescence in situ hybridization (3D-FISH). Exp Cell Res 276:10–23

    Article  PubMed  CAS  Google Scholar 

  • Strouboulis J, Wolffe AP (1996) Functional compartmentalization of the nucleus. J Cell Sci 109:1991–2000

    PubMed  CAS  Google Scholar 

  • Tanabe H, Habermann FA, Solovei I, Cremer M, Cremer T (2002a) Non-random radial arrangements of interphase chromosome territories: evolutionary considerations and functional implications. Mutat Res 504:37–45

    PubMed  CAS  Google Scholar 

  • Tanabe H, Muller S, Neusser M, von Hase J, Calcagno E, Cremer M, Solovei I, Cremet C, Cremer T (2002b) Evolutionary conservation of chromosome territory arrangements in cell nuclei from higher primates. Proc Natl Acad Sci USA 99:4424–4429

    Article  PubMed  CAS  Google Scholar 

  • Volpi EV, Chevret E, Jones T, Vatcheva R, Williamson J, Beck S, Campbell RD, Goldsworthy M, Powis SH, Ragoussis J, Trowsdale J, Sheer D (2000) Large-scale chromatin organization of the major histocompatibility complex and other regions of human chromosome 6 and its response to interferon in interphase nuclei. J Cell Sci 113:1565–1576

    PubMed  CAS  Google Scholar 

  • Zhou J, Ermakova OV, Riblet R, Birshtein BK, Schildkraut CL (2002) Replication and subnuclear location dynamics of the immunoglobulin heavy-chain locus in B-lineage cells. Mol Cell Biol 22:4876–4889

    Article  PubMed  CAS  Google Scholar 

  • Zink D (2006) The temporal program of DNA replication: new insight into old question. Chromosoma 115:273–287

    Article  PubMed  CAS  Google Scholar 

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Acknowledgement

We thank Giorgio Bernardi for very useful comments, Joanna Bridger and Oliver Clay for critical reading of the manuscript, and the anonymous referees for constructive criticisms.

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Correspondence to Salvatore Saccone.

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Communicated by R. Allshire

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Federico, C., Cantarella, C.D., Di Mare, P. et al. The radial arrangement of the human chromosome 7 in the lymphocyte cell nucleus is associated with chromosomal band gene density. Chromosoma 117, 399–410 (2008). https://doi.org/10.1007/s00412-008-0160-x

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  • DOI: https://doi.org/10.1007/s00412-008-0160-x

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