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Gene regulation and large-scale chromatin organization in the nucleus

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Abstract

Regulation of gene expression involves a number of different levels of organization in the cell nucleus. The main agents of transcriptional control are the cis-acting sequences in the immediate vicinity of a gene, which combine to form the functional unit or domain. Contacts between these sequences through the formation of chromatin loops forms the most basic level of organization. The activity of functional domains is also influenced by higher order chromatin structures that impede or permit access of factors to the genes. Epigenetic modifications can maintain and propagate these active or repressive chromatin structures across large genomic regions or even entire chromosomes. There is also evidence that transcription is organized into structures called ‘factories’ and that this can lead to inter-chromosomal contacts between genes that have the potential to influence their regulation.

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References

  • Andrulis E, Neiman A, Zappulla D, Sternglatz R (1998) Perinuclear localisation of chromatin facilitates transcriptional silencing. Nature 394: 592–595.

    CAS  PubMed  Google Scholar 

  • Anguita E, Johnson CA, Wood WG, Turner BM, Higgs DR (2001) Identification of a conserved erythroid specific domain of histone acetylation across the alpha-globin gene cluster. Proc Natl Acad Sci USA 98: 12114–12119.

    Article  CAS  PubMed  Google Scholar 

  • Belmont A, Dietzel S, Nye A, Strukov Y, Tumbar T (1999) Large scale chromatin structure and function. Curr Opin Cell Biol 11: 307–311.

    Article  CAS  PubMed  Google Scholar 

  • Boyes J, Felsenfeld G (1996) Tissue-specific factors additively increase the probability of the all-or-none formation of a hypersensitive site. EMBO J 15: 2496–2507.

    CAS  PubMed  Google Scholar 

  • Bulger M, van Doorninck JH, Saitoh N et al. (1999) Conservation of sequence and structure flanking the mouse and human beta-globin loci: the beta-globin genes are embedded within an array of odorant receptor genes. Proc Natl Acad Sci USA 96: 5129–5134.

    Article  CAS  PubMed  Google Scholar 

  • Burgess-Beusse B, Farrell C, Gaszner M et al. (2002) The insulation of genes from external enhancers and silencing chromatin. Proc Natl Acad Sci USA 99: 16433–16437.

    Google Scholar 

  • Bystricky K, Heun P, Gehlen L, Langowski J, Gasser SM (2004) Long-range compaction and flexibility of interphase chromatin in budding yeast analyzed by high-resolution imaging techniques. Proc Natl Acad Sci USA 101: 16495–16500.

    Article  CAS  PubMed  Google Scholar 

  • Cajiao I, Zhang A, Yoo EJ, Cooke NE, Liebhaber SA (2004) Bystander gene activation by a locus control region. EMBO J 23: 3854–3863.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Carpenter A, Memedula S, Plutz M, Belmont A (2004) Common effects of acidic activators on large-scale chromatin structure and transcription. Mol Cell Biol 25: 958–968.

    Google Scholar 

  • Carter D, Chakalova L, Osborne CS, Dai YF, Fraser P (2002) Long-range chromatin regulatory interactions in vivo. Nat Genet 32: 623–626.

    Article  CAS  PubMed  Google Scholar 

  • Casolari JM, Brown CR, Komili S, West J, Hieronymus H, Silver PA (2004) Genome-wide localization of the nuclear transport machinery couples transcriptional status and nuclear organization. Cell 117: 427–439.

    Article  CAS  PubMed  Google Scholar 

  • Chambeyron S, Bickmore W (2004) Chromatin decondensation and nuclear reorganization of the HoxB locus upon induction of transcription. Genes Dev 18: 1119–1130.

    Article  CAS  PubMed  Google Scholar 

  • Cheutin T, McNairn A, Jenuwein T, Gilbert D, Singh P, Misteli T (2003) Maintenance of stable heterochromatin domains by dynamic HP1 binding. Science 299: 721–725.

    Article  CAS  PubMed  Google Scholar 

  • Chong S, Riggs AD, Bonifer C (2002) The chicken lysozyme chromatin domain contains a second, widely expressed gene. Nucleic Acids Res 30(2): 463–467.

    Article  CAS  PubMed  Google Scholar 

  • Dillon N (2003) Gene autonomy: position effects continue to raise questions about the physical structure of the particulate Mendelian gene. Nature 425: 457.

    Article  CAS  PubMed  Google Scholar 

  • Dillon N, Sabbattini P (2000) Functional gene expression domains: defining the functional unit of gene regulation. BioEssays 22: 657–665.

    Article  CAS  PubMed  Google Scholar 

  • Dillon N, Trimborn T, Strouboulis J, Fraser P, Grosveld F (1997) The effect of distance on long-range chromatin interactions. Mol Cell 1: 131–139.

    Article  CAS  PubMed  Google Scholar 

  • Dorigo B, Schalch T, Kulangara A, Duda S, Schroeder RR, Richmond TJ (2004) Nucleosome arrays reveal the two-start organization of the chromatin fiber. Science 306: 1571–1573.

    Article  CAS  PubMed  Google Scholar 

  • Elgin SC (1996) Heterochromatin and gene regulation in Drosophila. Curr Opin Genet Dev 6: 193–202.

    Article  CAS  PubMed  Google Scholar 

  • Epner E, Reik A, Cimbora D et al. (1998) The β-globin LCR is not necessary for an open chromatin structure or developmentally regulated transcription of the mouse β-globin locus. Mol Cell 2: 447–455.

    Article  CAS  PubMed  Google Scholar 

  • Festenstein R, Tolaini M, Corbella P et al. (1996) Locus control region function and heterochromatin-induced position effect variegation. Science 271: 1123–1125.

    CAS  PubMed  Google Scholar 

  • Festenstein R, Pagakis S, Hiragami K et al. (2003) Modulation of heterochromatin protein 1 dynamics in primary mammalian cells. Science 299: 719–721.

    Article  CAS  PubMed  Google Scholar 

  • Fourel G, Magdinier F, Gilson E (2004) Insulator dynamics and the setting of chromatin domains. Bioessays 26: 523–532.

    Article  CAS  PubMed  Google Scholar 

  • Gottschling D, Aparicio O, Billington B, Zakian V (1990) Position effect at S. cerevisiae telomeres: reversible repression of Pol II transcription. Cell 63: 751–762.

    Article  CAS  PubMed  Google Scholar 

  • Greaves DR, Wilson FD, Lang G, Kioussis D (1989) Human CD2 3′-flanking sequences confer high-level, T cell-specific, position-independent gene expression in transgenic mice. Cell 56: 979–986.

    Article  CAS  PubMed  Google Scholar 

  • Grewal SI, Rice JC (2004) Regulation of heterochromatin by histone methylation and small RNAs. Curr Opin Cell Biol 16: 230–238.

    Article  CAS  PubMed  Google Scholar 

  • Grosveld F, van Assendelft GB, Greaves DR, Kollias G (1987) Position-independent, high-level expression of the human beta-globin gene in transgenic mice. Cell 51: 975–985.

    Article  CAS  PubMed  Google Scholar 

  • Grummt I (2003) Life on a planet of its own: regulation of RNA polymerase I transcription in the nucleolus. Genes Dev 17: 1691–1702.

    Article  CAS  PubMed  Google Scholar 

  • Haynes KA, Leibovitch BA, Rangwala SH, Craig C, Elgin SC (2004) Analyzing heterochromatin formation using chromosome 4 of Drosophila melanogaster. Cold Spring Harbor Symp Quant Biol 69: 267–272.

    CAS  PubMed  Google Scholar 

  • Heard E (2004) Recent advances in X-chromosome inactivation. Curr Opin Cell Biol 16: 247–255.

    Article  CAS  PubMed  Google Scholar 

  • Hetzer M, Walther, TC, Mattaj IW (2005) Pushing the envelope: structure, function, and dynamics of the nuclear periphery. Annu Rev Cell Dev Biol 21: 347–380.

    Article  CAS  PubMed  Google Scholar 

  • Heun P, Taddei A, Gasser SM (2001) From snapshots to moving pictures: new perspectives on nuclear organization. Trends Cell Biol 11: 519–525.

    Article  CAS  PubMed  Google Scholar 

  • Kelley RL (2004) Path to equality strewn with roX. Dev Biol 269: 18–25.

    Article  CAS  PubMed  Google Scholar 

  • Kimura H, Sugaya K, Cook PR (2002) The transcription cycle of RNA polymerase II in living cells. J Cell Biol 159: 777–782.

    Article  CAS  PubMed  Google Scholar 

  • Krajewski W, Becker PB (1998) Reconstitution of hyperacetylated, DNase I-sensitive chromatin characterized by high conformational flexibility of nucleosomal DNA. EMBO Rep 95: 1540–1545.

    CAS  Google Scholar 

  • Labrador M, Corces VG (2002) Setting the boundaries of chromatin domains and nuclear organization. Cell 111: 151–154.

    Article  CAS  PubMed  Google Scholar 

  • Litt MD, Simpson M, Recillas-Targa F, Prioleau MN, Felsenfeld G (2001) Transitions in histone acetylation reveal boundaries of three separately regulated neighboring loci. EMBO J 20: 2224–2235.

    Article  CAS  PubMed  Google Scholar 

  • Lundgren M, Chow C, Sabbattini P, Georgiou A, Minaee S, Dillon N (2000) Transcription factor dosage affects changes in higher order chromatin structure associated with activation of a heterochromatic gene. Cell 103: 733–743.

    Article  CAS  PubMed  Google Scholar 

  • Mahy NL, Perry PE, Gilchrist S, Baldock RA, Bickmore WA (2002) Spatial organization of active and inactive genes and noncoding DNA within chromosome territories. J Cell Biol 157: 579–589.

    Article  CAS  PubMed  Google Scholar 

  • Marshall WF, Straight A, Marko JF et al. (1997) Interphase chromosomes undergo constrained diffusional motion in living cells. Curr Biol 7: 930–939.

    Article  CAS  PubMed  Google Scholar 

  • Martin S, Pombo A (2003) Transcription factories: quantitative studies of nanostructures in the mammalian nucleus. Chromosome Res 11: 461–470.

    Article  CAS  PubMed  Google Scholar 

  • Mayer C, Grummt I (2005) Cellular stress and nucleolar function. Cell Cycle 4: 1036–1038.

    PubMed  Google Scholar 

  • McNally J, Muller W, Walker D, Wolford R, Hager G (2000) The glucocorticoid receptor: rapid exchange with regulatory sites in living cells. Science 287: 1262–1265.

    Article  CAS  PubMed  Google Scholar 

  • Milot E, Strouboulis J, Trimborn T et al. (1996) Heterochromatin effects on the frequency and duration of LCR-mediated gene transcription. Cell 87: 105–114.

    Article  CAS  PubMed  Google Scholar 

  • Minaee S, Farmer D, Georgiou A et al. (2005) Mapping and functional analysis of regulatory sequences in the mouse lambda5-VpreB1 domain. Mol Immunol 42: 1283–1292.

    Article  CAS  PubMed  Google Scholar 

  • Osborne C, Chakalova L, Brown K et al. (2004) Active genes dynamically colocalize to shared sites of ongoing transcription. Nat Genet 36: 1065–1071.

    Article  CAS  PubMed  Google Scholar 

  • Ovcharenko I, Loots GG, Nobrega MA, Hardison RC, Miller W, Stubbs L (2005) Evolution and functional classification of vertebrate gene deserts. Genome Res 15: 137–145.

    CAS  PubMed  Google Scholar 

  • Peters AH, Schubeler D (2005) Methylation of histones: playing memory with DNA. Curr Opin Cell Biol 17: 230–238.

    CAS  PubMed  Google Scholar 

  • Peters A, Kubicek S, Mechtler K et al. (2003) Partitioning and plasticity of repressive histone methylation states in mammalian chromatin. Mol Cell 12: 1577–1589.

    Article  CAS  PubMed  Google Scholar 

  • Philipsen S, Pruzina S, Grosveld F (1993) The minimal requirements for activity in transgenic mice of hypersensitive site 3 of the beta globin locus control region. EMBO J 12: 1077–1085.

    CAS  PubMed  Google Scholar 

  • Raska I, Koberna K, Malinsky J, Fidlerova H, and Masata M (2004) The nucleolus and transcription of ribosomal genes. Biol Cell 96: 579–594.

    Article  CAS  PubMed  Google Scholar 

  • Sabbattini P, Georgiou A, Sinclair C, Dillon N (1999) Analysis of mice with single copies and multiple copies of transgenes reveals a novel arrangement for the λ5-VpreB1 locus control region. Mol Cell Biol 19: 671–679.

    CAS  PubMed  Google Scholar 

  • Schalch T, Duda S, Sargent DF, Richmond TJ (2005) X-ray structure of a tetranucleosome and its implications for the chromatin fibre. Nature 436: 138–141.

    Article  CAS  PubMed  Google Scholar 

  • Silva J, Mak W, Zvetkova I et al. (2003) Establishment of histone H3 methylation on the inactive X chromosome requires transient recruitment of Eed–Enx1 polycomb group complexes. Dev Cell 4: 481–495.

    Article  CAS  PubMed  Google Scholar 

  • Singer G, Lloyd A, Huminiecki L, Wolfe K (2005) Clusters of co-expressed genes in mammalian genomes are conserved by natural selection. Mol Biol Evol 22: 767–775.

    CAS  PubMed  Google Scholar 

  • Spellman PT, Rubin GM (2002) Evidence for large domains of similarly expressed genes in the Drosophila genome. J Biol 1: 5.

    Article  PubMed  Google Scholar 

  • Spilianakis C, Lalioti M, Town T, Lee G, Flavell R (2005) Interchromosomal associations between alternatively expressed loci. Nature 435: 637–645.

    Article  CAS  PubMed  Google Scholar 

  • Spradling AC (1994) Transposable elements and the evolution of heterochromatin. Soc Gen Physiol Ser 49: 69–83.

    CAS  PubMed  Google Scholar 

  • Szutorisz H, Canzonetta C, Georgiou A, Chow, C-M, Tora L, Dillon N (2005a). Formation of an active tissue-specific chromatin domain initiated by epigenetic marking at the embryonic stem cell stage. Mol Cell Biol 25: 1804–1820.

    Article  CAS  PubMed  Google Scholar 

  • Szutorisz H, Dillon N, Tora L (2005b) The role of enhancers as centres for general transcription factor recruitment. Trends Biochem Sci 30: 593–599.

    Article  CAS  PubMed  Google Scholar 

  • Tolhuis B, Palstra RJ, Splinter E, Grosveld F, de Laat W (2002) Looping and interaction between hypersensitive sites in the active beta-globin locus. Mol Cell 10: 1453–1465.

    Article  CAS  PubMed  Google Scholar 

  • Verschure PJ, van Der Kraan I, Manders EM, van Driel R (1999) Spatial relationship between transcription sites and chromosome territories. J Cell Biol 147: 13–24.

    Article  CAS  PubMed  Google Scholar 

  • Vogel J, von Heydebreck A, Purmann A, Sperling S (2005) Chromosomal clustering of a human transcriptome reveals regulatory background. BMC Bioinformatics 19: 6:230.

    Google Scholar 

  • Wallrath L, Elgin S (1995) Position effect variegation in Drosophila is associated with an altered chromatin structure. Genes Dev 9: 1263–1267.

    CAS  PubMed  Google Scholar 

  • Weiler K, Wakimoto B (1995) Heterochromatin and gene expression in Drosophila. Annu Rev Genet 29: 577–605.

    Article  CAS  PubMed  Google Scholar 

  • Williams RR (2003) Transcription and the territory: the ins and outs of gene positioning. Trends Genet 19: 298–302.

    Article  CAS  PubMed  Google Scholar 

  • Woodcock CL, Dimitrov S (2001) Higher-order structure of chromatin and chromosomes. Curr Opin Genet Dev 11: 130–135.

    Article  CAS  PubMed  Google Scholar 

  • Woodcock CL, Frado LL, Rattner JB (1984) The higher-order structure of chromatin: evidence for a helical ribbon arrangement. J Cell Biol 99: 42–52.

    Article  CAS  PubMed  Google Scholar 

  • Yang XJ (2004) Lysine acetylation and the bromodomain: a new partnership for signaling. BioEssays 26: 1076–1087.

    Article  CAS  PubMed  Google Scholar 

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  1. Gene Regulation and Chromatin Group, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Campus, Du Cane Road, London, W12 ONN, UK

    Niall Dillon

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Dillon, N. Gene regulation and large-scale chromatin organization in the nucleus. Chromosome Res 14, 117–126 (2006). https://doi.org/10.1007/s10577-006-1027-8

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