The nuclear envelope in genome organization, expression and stability

Non-random positioning of chromosomal domains relative to each other and to nuclear landmarks is a common feature of eukaryotic genomes. In particular, the distribution of DNA loci relative to the nuclear periphery has been linked to both transcriptional activation and repression. Nuclear pores and other integral membrane protein complexes are key players in the dynamic organization of the genome in the nucleus, and recent advances in our understanding of the molecular networks that organize genomes at the nuclear periphery point to a further role for non-random locus positioning in DNA repair, recombination and stability.

[1]  A. Straight,et al.  Net1, a Sir2-Associated Nucleolar Protein Required for rDNA Silencing and Nucleolar Integrity , 1999, Cell.

[2]  Angelika Amon,et al.  Cfi1 prevents premature exit from mitosis by anchoring Cdc14 phosphatase in the nucleolus , 1999, Nature.

[3]  M. Ladurner,et al.  The nuclear envelope protein Matefin/SUN-1 is required for homologous pairing in C. elegans meiosis. , 2007, Developmental cell.

[4]  K. Wilson,et al.  Emerin Caps the Pointed End of Actin Filaments: Evidence for an Actin Cortical Network at the Nuclear Inner Membrane , 2004, PLoS biology.

[5]  S. Gasser,et al.  Sir-Mediated Repression Can Occur Independently of Chromosomal and Subnuclear Contexts , 2004, Cell.

[6]  E. Gilson,et al.  SIR3 and SIR4 proteins are required for the positioning and integrity of yeast telomeres , 1993, Cell.

[7]  Anne E Carpenter,et al.  Long-Range Directional Movement of an Interphase Chromosome Site , 2006, Current Biology.

[8]  J. Conchello,et al.  Rapid Telomere Movement in Meiotic Prophase Is Promoted By NDJ1, MPS3, and CSM4 and Is Modulated by Recombination , 2008, Cell.

[9]  J. Bader,et al.  A DNA Integrity Network in the Yeast Saccharomyces cerevisiae , 2013, Cell.

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

[11]  David A. Agard,et al.  Three-dimensional architecture of a polytene nucleus , 1983, Nature.

[12]  W. L. Fangman,et al.  A replication fork barrier at the 3′ end of yeast ribosomal RNA genes , 1988, Cell.

[13]  D. Moazed,et al.  Association of the RENT complex with nontranscribed and coding regions of rDNA and a regional requirement for the replication fork block protein Fob1 in rDNA silencing. , 2003, Genes & development.

[14]  J. Pérez-Ortín,et al.  The inner nuclear membrane protein Src1 associates with subtelomeric genes and alters their regulated gene expression , 2008, The Journal of cell biology.

[15]  Elizabeth Kerr,et al.  Recruitment to the Nuclear Periphery Can Alter Expression of Genes in Human Cells , 2008, PLoS genetics.

[16]  Juan M. Vaquerizas,et al.  Nuclear Pore Proteins Nup153 and Megator Define Transcriptionally Active Regions in the Drosophila Genome , 2010, PLoS genetics.

[17]  Philippe Debeer,et al.  Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis , 2004, Nature Genetics.

[18]  J. Boeke,et al.  An unusual form of transcriptional silencing in yeast ribosomal DNA. , 1997, Genes & development.

[19]  John R Yates,et al.  Nuclear Membrane Proteins with Potential Disease Links Found by Subtractive Proteomics , 2003, Science.

[20]  S. Gygi,et al.  Inhibition of homologous recombination by a cohesin-associated clamp complex recruited to the rDNA recombination enhancer. , 2006, Genes & development.

[21]  M. Yanagida,et al.  Cell cycle-dependent specific positioning and clustering of centromeres and telomeres in fission yeast , 1993, The Journal of cell biology.

[22]  Abena B. Redwood,et al.  Novel roles for A‐type lamins in telomere biology and the DNA damage response pathway , 2009, EMBO Journal.

[23]  M. Blasco.  The epigenetic regulation of mammalian telomeres , 2007, Nature Reviews Genetics.

[24]  M. Gustafsson,et al.  Subdiffraction Multicolor Imaging of the Nuclear Periphery with 3D Structured Illumination Microscopy , 2008, Science.

[25]  P. Walter,et al.  Gene Recruitment of the Activated INO1 Locus to the Nuclear Membrane , 2004, PLoS biology.

[26]  P. Sung,et al.  Mechanism of homologous recombination: mediators and helicases take on regulatory functions , 2006, Nature Reviews Molecular Cell Biology.

[27]  Ulrich Wagner,et al.  Chromatin-Bound Nuclear Pore Components Regulate Gene Expression in Higher Eukaryotes , 2010, Cell.

[28]  Austen R. D. Ganley,et al.  Recombination Regulation by Transcription-Induced Cohesin Dissociation in rDNA Repeats , 2005, Science.

[29]  M. Gartenberg.  Life on the edge: telomeres and persistent DNA breaks converge at the nuclear periphery. , 2009, Genes & development.

[30]  Daniel A Starr.  A nuclear-envelope bridge positions nuclei and moves chromosomes , 2009, Journal of Cell Science.

[31]  Jef D. Boeke,et al.  A Genetic Screen for Ribosomal DNA Silencing Defects Identifies Multiple DNA Replication and Chromatin-Modulating Factors , 1999, Molecular and Cellular Biology.

[32]  A. Dernburg,et al.  Cytoskeletal Forces Span the Nuclear Envelope to Coordinate Meiotic Chromosome Pairing and Synapsis , 2009, Cell.

[33]  E. Gilson,et al.  Identification of a perinuclear positioning element in human subtelomeres that requires A‐type lamins and CTCF , 2009, The EMBO journal.

[34]  T. Kobayashi,et al.  A yeast gene product, Fob1 protein, required for both replication fork blocking and recombinational hotspot activities , 1996, Genes to cells : devoted to molecular & cellular mechanisms.

[35]  S. Gasser,et al.  Repairing subtelomeric DSBs at the nuclear periphery. , 2006, Trends in cell biology.

[36]  M. Resnick,et al.  Genes required for ionizing radiation resistance in yeast , 2001, Nature Genetics.

[37]  M. Kenna,et al.  The Nuclear Envelope and Spindle Pole Body-Associated Mps3 Protein Bind Telomere Regulators and Function in Telomere Clustering , 2007, Cell cycle.

[38]  M. Prentiss,et al.  Meiotic Chromosomes Move by Linkage to Dynamic Actin Cables with Transduction of Force through the Nuclear Envelope , 2008, Cell.

[39]  S. Gygi,et al.  Role for perinuclear chromosome tethering in maintenance of genome stability , 2008, Nature.

[40]  V. Corces,et al.  The nuclear pore complex and chromatin boundaries. , 2002, Trends in cell biology.

[41]  G. Roeder,et al.  Cis-acting, recombination-stimulating activity in a fragment of the ribosomal DNA of S. cerevisiae , 1984, Cell.

[42]  R. Sternglanz,et al.  Esc1, a Nuclear Periphery Protein Required for Sir4-Based Plasmid Anchoring and Partitioning , 2002, Molecular and Cellular Biology.

[43]  S. Jentsch,et al.  Chromosome-wide Rad51 spreading and SUMO-H2A.Z-dependent chromosome fixation in response to a persistent DNA double-strand break. , 2009, Molecular cell.

[44]  Grant W. Brown,et al.  Functional Targeting of DNA Damage to a Nuclear Pore-Associated SUMO-Dependent Ubiquitin Ligase , 2008, Science.

[45]  Sara Ahmed,et al.  DNA zip codes control an ancient mechanism for gene targeting to the nuclear periphery , 2010, Nature Cell Biology.

[46]  M. Nomura.  Ribosomal RNA genes, RNA polymerases, nucleolar structures, and synthesis of rRNA in the yeast Saccharomyces cerevisiae. , 2001, Cold Spring Harbor symposia on quantitative biology.

[47]  Robert J. D. Reid,et al.  The Smc5–Smc6 complex and SUMO modification of Rad52 regulates recombinational repair at the ribosomal gene locus , 2007, Nature Cell Biology.

[48]  P. Silver,et al.  Global histone acetylation induces functional genomic reorganization at mammalian nuclear pore complexes. , 2008, Genes & development.

[49]  L. Gunaratnam,et al.  Regulation of ubiquitin ligase dynamics by the nucleolus , 2005, The Journal of cell biology.

[50]  G. Ammerer,et al.  Meiotic Chromosome Homology Search Involves Modifications of the Nuclear Envelope Protein Matefin/SUN-1 , 2009, Cell.

[51]  C. Stewart,et al.  Transmembrane protein Sun2 is involved in tethering mammalian meiotic telomeres to the nuclear envelope , 2007, Proceedings of the National Academy of Sciences.

[52]  Y. Hiraoka,et al.  Meiotic Proteins Bqt1 and Bqt2 Tether Telomeres to Form the Bouquet Arrangement of Chromosomes , 2006, Cell.

[53]  E. Gilson,et al.  The DNA damage response at eroded telomeres and tethering to the nuclear pore complex , 2009, Nature Cell Biology.

[54]  S. Henikoff,et al.  Identification of in vivo DNA targets of chromatin proteins using tethered Dam methyltransferase , 2000, Nature Biotechnology.

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

[56]  J W Sedat,et al.  Spatial organization of chromosomes in the salivary gland nuclei of Drosophila melanogaster , 1986, The Journal of cell biology.

[57]  Anna Shevchenko,et al.  Exit from Mitosis Is Triggered by Tem1-Dependent Release of the Protein Phosphatase Cdc14 from Nucleolar RENT Complex , 1999, Cell.

[58]  R. Reddel,et al.  The first molecular details of ALT in human tumor cells. , 2005, Human molecular genetics.

[59]  R. Foisner,et al.  LEM2 is a novel MAN1-related inner nuclear membrane protein associated with A-type lamins , 2005, Journal of Cell Science.

[60]  J. Olivo-Marin,et al.  Nuclear architecture and spatial positioning help establish transcriptional states of telomeres in yeast , 2002, Nature Cell Biology.

[61]  J. Pérez-Ortín,et al.  SRC1: an intron‐containing yeast gene involved in sister chromatid segregation , 2002, Yeast.

[62]  E. Maestrini,et al.  Identification of a novel X-linked gene responsible for Emery-Dreifuss muscular dystrophy , 1994, Nature Genetics.

[63]  M. Fornerod,et al.  Nucleoporins Directly Stimulate Expression of Developmental and Cell-Cycle Genes Inside the Nucleoplasm , 2010, Cell.

[64]  A. Miele,et al.  Mechanisms that regulate localization of a DNA double-strand break to the nuclear periphery. , 2009, Genes & development.

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

[66]  Peter Teague,et al.  Differences in the Localization and Morphology of Chromosomes in the Human Nucleus , 1999, The Journal of cell biology.

[67]  S. Gasser,et al.  The nuclear envelope and transcriptional control , 2007, Nature Reviews Genetics.

[68]  M. Fornerod,et al.  Characterization of the Drosophila melanogaster genome at the nuclear lamina , 2006, Nature Genetics.

[69]  Yuda Fang,et al.  Centromere positioning and dynamics in living Arabidopsis plants. , 2005, Molecular biology of the cell.

[70]  R. E. Esposito,et al.  Direct evidence for SIR2 modulation of chromatin structure in yeast rDNA , 1997, The EMBO journal.

[71]  T. Cech,et al.  Telomerase and DNA end replication: no longer a lagging strand problem? , 1995, Science.

[72]  F. Hediger,et al.  Nuclear pore association confers optimal expression levels for an inducible yeast gene , 2006, Nature.

[73]  Florence Hediger,et al.  Separation of silencing from perinuclear anchoring functions in yeast Ku80, Sir4 and Esc1 proteins , 2004, The EMBO journal.

[74]  Guennaelle Dieppois,et al.  Cotranscriptional Recruitment to the mRNA Export Receptor Mex67p Contributes to Nuclear Pore Anchoring of Activated Genes , 2006, Molecular and Cellular Biology.

[75]  R. E. Esposito,et al.  A new role for a yeast transcriptional silencer gene, SIR2, in regulation of recombination in ribosomal DNA , 1989, Cell.

[76]  Michael E Dresser,et al.  MPS3 mediates meiotic bouquet formation in Saccharomyces cerevisiae , 2007, Proceedings of the National Academy of Sciences.

[77]  K. Wilson,et al.  MAN1 and emerin have overlapping function(s) essential for chromosome segregation and cell division in Caenorhabditis elegans , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[78]  T. Richmond,et al.  Crystal structure of the nucleosome core particle at 2.8 Å resolution , 1997, Nature.

[79]  D. Moazed.  Small RNAs in transcriptional gene silencing and genome defence , 2009, Nature.

[80]  Jean-Christophe Olivo-Marin,et al.  Nuclear pore complexes in the organization of silent telomeric chromatin , 2000, Nature.

[81]  B. Dujon,et al.  Genetic network interactions among replication, repair and nuclear pore deficiencies in yeast. , 2005, DNA repair.

[82]  K. P. Rabitsch,et al.  Kinetochore recruitment of two nucleolar proteins is required for homolog segregation in meiosis I. , 2003, Developmental cell.

[83]  Min Han,et al.  Role of ANC-1 in Tethering Nuclei to the Actin Cytoskeleton , 2002, Science.

[84]  A. Gregory Matera,et al.  Actin-dependent intranuclear repositioning of an active gene locus in vivo , 2007, The Journal of cell biology.

[85]  B. Dujon,et al.  Telomere tethering at the nuclear periphery is essential for efficient DNA double strand break repair in subtelomeric region , 2006, The Journal of cell biology.

[86]  Susan M. Gasser,et al.  Live Imaging of Telomeres yKu and Sir Proteins Define Redundant Telomere-Anchoring Pathways in Yeast , 2002, Current Biology.

[87]  S. Gasser,et al.  The nuclear envelope--a scaffold for silencing? , 2009, Current opinion in genetics & development.

[88]  Florence Hediger,et al.  Myosin-like proteins 1 and 2 are not required for silencing or telomere anchoring, but act in the Tel1 pathway of telomere length control. , 2002, Journal of structural biology.

[89]  V. Andrés,et al.  Role of A-type lamins in signaling, transcription, and chromatin organization , 2009, The Journal of cell biology.

[90]  S. Jaspersen,et al.  Telomere anchoring at the nuclear periphery requires the budding yeast Sad1-UNC-84 domain protein Mps3 , 2007, The Journal of cell biology.

[91]  E. Bertolino,et al.  Transcriptional repression mediated by repositioning of genes to the nuclear lamina , 2008, Nature.

[92]  G. Blobel,et al.  A Network of Nuclear Envelope Membrane Proteins Linking Centromeres to Microtubules , 2008, Cell.

[93]  Peter Fraser,et al.  Gene regulation through nuclear organization , 2007, Nature Structural &Molecular Biology.

[94]  K. S. Egorova,et al.  The B-type lamin is required for somatic repression of testis-specific gene clusters , 2009, Proceedings of the National Academy of Sciences.

[95]  F. Alt,et al.  Pathways that suppress programmed DNA breaks from progressing to chromosomal breaks and translocations. , 2006, DNA repair.

[96]  M. Gartenberg,et al.  Persistence of an alternate chromatin structure at silenced loci in vitro. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[97]  E. Gilson,et al.  Evidence for silencing compartments within the yeast nucleus: a role for telomere proximity and Sir protein concentration in silencer-mediated repression. , 1996, Genes & development.

[98]  W. Z. Cande,et al.  Bqt2p is essential for initiating telomere clustering upon pheromone sensing in fission yeast , 2006, The Journal of cell biology.

[99]  L. Wessels,et al.  Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions , 2008, Nature.

[100]  S. Gasser,et al.  Yeast telomerase and the SUN domain protein Mps3 anchor telomeres and repress subtelomeric recombination. , 2009, Genes & development.

[101]  F. Hediger,et al.  The function of telomere clustering in yeast: the circe effect. , 2004, Cold Spring Harbor symposia on quantitative biology.

[102]  D. Moazed,et al.  Common themes in mechanisms of gene silencing. , 2001, Molecular cell.

[103]  D. Garfinkel,et al.  Transcriptional silencing of Ty1 elements in the RDN1 locus of yeast. , 1997, Genes & development.

[104]  Francis S. Collins,et al.  Human laminopathies: nuclei gone genetically awry , 2006, Nature Reviews Genetics.

[105]  Xianpeng Liu,et al.  Nucleoporins prevent DNA damage accumulation by modulating Ulp1-dependent sumoylation processes. , 2007, Molecular biology of the cell.

[106]  U. K. Laemmli,et al.  Chromatin Boundaries in Budding Yeast The Nuclear Pore Connection , 2002, Cell.

[107]  E. Gilson,et al.  Subtelomeric factors antagonize telomere anchoring and Tel1‐independent telomere length regulation , 2006, The EMBO journal.

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

[109]  Min Han,et al.  SUN1 is required for telomere attachment to nuclear envelope and gametogenesis in mice. , 2007, Developmental cell.

[110]  Jean-Christophe Olivo-Marin,et al.  SAGA interacting factors confine sub-diffusion of transcribed genes to the nuclear envelope , 2006, Nature.

[111]  D. Comings,et al.  Arrangement of chromatin in the nucleus , 1980, Human Genetics.

[112]  J. Ellenberg,et al.  Mapping the dynamic organization of the nuclear pore complex inside single living cells , 2004, Nature Cell Biology.

[113]  S. Henikoff,et al.  Genetic modification of heterochromatic association and nuclear organization in Drosophila , 1996, Nature.

[114]  G. Blobel,et al.  Mlp-dependent anchorage and stabilization of a desumoylating enzyme is required to prevent clonal lethality , 2004, The Journal of cell biology.

[115]  Y. Hiraoka,et al.  Membrane proteins Bqt3 and -4 anchor telomeres to the nuclear envelope to ensure chromosomal bouquet formation , 2009, The Journal of cell biology.

[116]  D. Spector,et al.  A genetic locus targeted to the nuclear periphery in living cells maintains its transcriptional competence , 2008, The Journal of cell biology.