Telomere Position Effect in Human Cells

In yeast, telomere position effect (TPE) results in the reversible silencing of genes near telomeres. Here we demonstrate the presence of TPE in human cells. HeLa clones containing a luciferase reporter adjacent to a newly formed telomere express 10 times less luciferase than do control clones generated by random integration. Luciferase expression is restored by trichostatin A, a histone deacetylase inhibitor. Overexpression of a human telomerase reverse transcriptase complementary DNA results in telomere elongation and an additional 2- to 10-fold decrease in expression in telomeric clones but not control clones. The dependence of TPE on telomere length provides a mechanism for the modification of gene expression throughout the replicative life-span of human cells.

[1]  Jie Xu,et al.  Advances in molecular cytogenetics for the evaluation of mental retardation , 2003, American journal of medical genetics. Part C, Seminars in medical genetics.

[2]  M. Oshimura,et al.  Human chromosome 5 carries a putative telomerase repressor gene , 2003, Genes, chromosomes & cancer.

[3]  Michael Litt,et al.  The insulation of genes from external enhancers and silencing chromatin , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[4]  J. Lingner,et al.  Telomerase: biochemical considerations for enzyme and substrate. , 2002, Trends in biochemical sciences.

[5]  E. Gilson,et al.  Human telomeric position effect is determined by chromosomal context and telomeric chromatin integrity , 2002, EMBO reports.

[6]  J. Shay,et al.  Human Telomerase and Its Regulation , 2002, Microbiology and Molecular Biology Reviews.

[7]  David A Jones,et al.  Reactivating the expression of methylation silenced genes in human cancer , 2002, Oncogene.

[8]  Michael R. Green,et al.  Inappropriate Gene Activation in FSHD A Repressor Complex Binds a Chromosomal Repeat Deleted in Dystrophic Muscle , 2002, Cell.

[9]  P. Russell,et al.  Telomere binding of checkpoint sensor and DNA repair proteins contributes to maintenance of functional fission yeast telomeres. , 2002, Genetics.

[10]  V. Rakyan,et al.  Metastable epialleles in mammals. , 2002, Trends in genetics : TIG.

[11]  T. Zglinicki.  Oxidative stress shortens telomeres , 2002 .

[12]  M. Pardue,et al.  Coevolution of the telomeric retrotransposons across Drosophila species. , 2002, Genetics.

[13]  Chao Wei,et al.  Effects of double-strand break repair proteins on vertebrate telomere structure , 2002, Nucleic Acids Res..

[14]  M. Hentze,et al.  c-Src-Mediated Phosphorylation of hnRNP K Drives Translational Activation of Specifically Silenced mRNAs , 2002, Molecular and Cellular Biology.

[15]  J. Derisi,et al.  The genome-wide expression response to telomerase deletion in Saccharomyces cerevisiae , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Jin-Qiu Zhou,et al.  Saccharomyces Rrm3p, a 5' to 3' DNA helicase that promotes replication fork progression through telomeric and subtelomeric DNA. , 2002, Genes & development.

[17]  R. Hennekam,et al.  Further delineation of the chromosome 14q terminal deletion syndrome. , 2002, American journal of medical genetics.

[18]  Eun Shik Choi,et al.  Fission yeast Rap1 homolog is a telomere-specific silencing factor and interacts with Taz1p. , 2002, Molecules and cells.

[19]  Ying Huang.  Transcriptional silencing in Saccharomyces cerevisiae and Schizosaccharomyces pombe. , 2002, Nucleic acids research.

[20]  J. Masters.  HeLa cells 50 years on: the good, the bad and the ugly , 2002, Nature Reviews Cancer.

[21]  S. Dupuis,et al.  Functional Multimerization of Human Telomerase Requires an RNA Interaction Domain in the N Terminus of the Catalytic Subunit , 2002, Molecular and Cellular Biology.

[22]  Heather C. Mefford,et al.  The complex structure and dynamic evolution of human subtelomeres , 2002, Nature Reviews Genetics.

[23]  R. Reddel,et al.  Alternative lengthening of telomeres in mammalian cells , 2002, Oncogene.

[24]  C. Harley.  Telomerase is not an oncogene , 2002, Oncogene.

[25]  W. Tham,et al.  Transcriptional silencing at Saccharomyces telomeres: implications for other organisms , 2002, Oncogene.

[26]  T. Lange.  Protection of mammalian telomeres , 2002, Oncogene.

[27]  Karol Bomsztyk,et al.  Yeast hnRNP K-Like Genes Are Involved in Regulation of the Telomeric Position Effect and Telomere Length , 2002, Molecular and Cellular Biology.

[28]  Stuart Schwartz,et al.  Human-specific duplication and mosaic transcripts: the recent paralogous structure of chromosome 22. , 2002, American journal of human genetics.

[29]  L. Guarente,et al.  Model organisms as a guide to mammalian aging. , 2002, Developmental cell.

[30]  N. Weng.  Regulation of telomerase expression in human lymphocytes , 2002, Springer Seminars in Immunopathology.

[31]  D R Bentley,et al.  The DNA sequence and comparative analysis of human chromosome 20 , 2004, Nature.

[32]  B. Armbruster,et al.  N-Terminal Domains of the Human Telomerase Catalytic Subunit Required for Enzyme Activity in Vivo , 2001, Molecular and Cellular Biology.

[33]  B. Trask,et al.  Comparative sequencing of a multicopy subtelomeric region containing olfactory receptor genes reveals multiple interactions between non-homologous chromosomes. , 2001, Human molecular genetics.

[34]  B. Trask,et al.  Transcriptional activity of multiple copies of a subtelomerically located olfactory receptor gene that is polymorphic in number and location. , 2001, Human molecular genetics.

[35]  G. Morin,et al.  TANK2, a New TRF1-associated Poly(ADP-ribose) Polymerase, Causes Rapid Induction of Cell Death upon Overexpression* , 2001, The Journal of Biological Chemistry.

[36]  M. Robinson,et al.  Functional Multimerization of the Human Telomerase Reverse Transcriptase , 2001, Molecular and Cellular Biology.

[37]  T. Miyakawa,et al.  Repression of rRNA synthesis due to a secretory defect requires the C-terminal silencing domain of Rap1p in Saccharomyces cerevisiae. , 2001, Nucleic acids research.

[38]  J. Shay,et al.  The La antigen associates with the human telomerase ribonucleoprotein and influences telomere length in vivo. , 2001, RNA.

[39]  I. Hope.  RNAi surges on: application to cultured mammalian cells. , 2001, Trends in genetics : TIG.

[40]  M. Amacker,et al.  Human telomerase contains two cooperating telomerase RNA molecules , 2001, The EMBO journal.

[41]  H. Biessmann,et al.  Terminal retrotransposons activate a subtelomeric white transgene at the 2L telomere in Drosophila. , 2001, Genetics.

[42]  C. Meijer,et al.  Telomerase suppression by chromosome 6 in a human papillomavirus type 16-immortalized keratinocyte cell line and in a cervical cancer cell line. , 2001, Journal of the National Cancer Institute.

[43]  E. Stanbridge,et al.  Microcell‐mediated transfer of chromosome 4 into HeLa cells suppresses telomerase activity , 2001, Genes, chromosomes & cancer.

[44]  B. Chabot,et al.  hnRNP A1 may interact simultaneously with telomeric DNA and the human telomerase RNA in vitro. , 2001, Nucleic acids research.

[45]  T. Tuschl,et al.  Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells , 2001, Nature.

[46]  G. Sutherland,et al.  Identification of a Novel Human Tankyrase through Its Interaction with the Adaptor Protein Grb14* , 2001, The Journal of Biological Chemistry.

[47]  Goberdhan P Dimri,et al.  Regulation of cellular senescence by p53. , 2001, European journal of biochemistry.

[48]  T. Suzuki,et al.  5-Bromodeoxyuridine suppresses position effect variegation of transgenes in HeLa cells. , 2001, Experimental cell research.

[49]  J. W. Turner,et al.  Stable Association of hsp90 and p23, but Not hsp70, with Active Human Telomerase* , 2001, The Journal of Biological Chemistry.

[50]  P. Baumann,et al.  Pot1, the Putative Telomere End-Binding Protein in Fission Yeast and Humans , 2001, Science.

[51]  B. Trask,et al.  Segmental duplications: organization and impact within the current human genome project assembly. , 2001, Genome research.

[52]  M. Vidal,et al.  Sequence and chromosomal context effects on variegated expression of keratin 5/lacZ constructs in stratified epithelia of transgenic mice. , 2001, Genetics.

[53]  P. Borst,et al.  Control of VSG gene expression sites. , 2001, Molecular and biochemical parasitology.

[54]  G. Starace,et al.  The length of telomeric G-rich strand 3'-overhang measured by oligonucleotide ligation assay. , 2001, Nucleic acids research.

[55]  S. Oikawa,et al.  Site-specific DNA damage at the GGG sequence by UVA involves acceleration of telomere shortening. , 2001, Biochemistry.

[56]  G. Thomas,et al.  Asp-Ala-His-Lys (DAHK) inhibits copper-induced oxidative DNA double strand breaks and telomere shortening. , 2001, Biochemical and biophysical research communications.

[57]  R. Moyzis,et al.  Integration of telomere sequences with the draft human genome sequence , 2001, Nature.

[58]  J. Peden,et al.  Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16. , 2001, Human molecular genetics.

[59]  J. Shay,et al.  Cellular senescence as a tumor-protection mechanism: the essential role of counting. , 2001, Current opinion in genetics & development.

[60]  M. Lagarkova,et al.  Cloning and characterization of TNKL, a member of tankyrase gene family , 2001, Genes and Immunity.

[61]  D. Lafontaine,et al.  Stable expression in yeast of the mature form of human telomerase RNA depends on its association with the box H/ACA small nucleolar RNP proteins Cbf5p, Nhp2p and Nop10p. , 2001, Nucleic acids research.

[62]  S. Gasser,et al.  A cytosolic NAD‐dependent deacetylase, Hst2p, can modulate nucleolar and telomeric silencing in yeast , 2001, The EMBO journal.

[63]  A. E. Kilburn,et al.  Insertion of a Telomere Repeat Sequence into a Mammalian Gene Causes Chromosome Instability , 2001, Molecular and Cellular Biology.

[64]  U. Fischer,et al.  Novel tankyrase-related gene detected with meningioma-specific sera. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[65]  J. M. Suh,et al.  Heterogeneous Nuclear Ribonucleoproteins C1 and C2 Associate with the RNA Component of Human Telomerase , 2000, Molecular and Cellular Biology.

[66]  W. Filipowicz,et al.  Human H / ACA Small Nucleolar RNPs and Telomerase Share Evolutionarily Conserved Proteins NHP 2 and NOP 10 , 2000 .

[67]  Thomas D. Schmittgen,et al.  Effect of experimental treatment on housekeeping gene expression: validation by real-time, quantitative RT-PCR. , 2000, Journal of biochemical and biophysical methods.

[68]  M. Hande,et al.  Ku acts in a unique way at the mammalian telomere to prevent end joining. , 2000, Genes & development.

[69]  T. Lange,et al.  Tankyrase promotes telomere elongation in human cells , 2000, Current Biology.

[70]  H. True,et al.  A yeast prion provides a mechanism for genetic variation and phenotypic diversity , 2000, Nature.

[71]  S. Lee,et al.  Interaction of human Ku70 with TRF2 , 2000, FEBS letters.

[72]  D. Higgs,et al.  alpha-thalassemia resulting from a negative chromosomal position effect. , 2000, Blood.

[73]  K. Collins,et al.  Human telomerase activation requires two independent interactions between telomerase RNA and telomerase reverse transcriptase. , 2000, Molecular cell.

[74]  J. Shay,et al.  Telomere dynamics in cancer progression and prevention: fundamental differences in human and mouse telomere biology , 2000, Nature Medicine.

[75]  I. Mian,et al.  Identification of Functionally Important Domains in the N-Terminal Region of Telomerase Reverse Transcriptase , 2000, Molecular and Cellular Biology.

[76]  J. Shay,et al.  Transient expression of human telomerase extends the life span of normal human fibroblasts. , 2000, Biochemical and biophysical research communications.

[77]  Matthias Mann,et al.  Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres , 2000, Nature Genetics.

[78]  J. Shay,et al.  Telomere Shortening Is Proportional to the Size of the G-rich Telomeric 3′-Overhang* , 2000, The Journal of Biological Chemistry.

[79]  Takashi Tsuruo,et al.  Involvement of 14‐3‐3 proteins in nuclear localization of telomerase , 2000, The EMBO journal.

[80]  T. Lange,et al.  Identification of Human Rap1 Implications for Telomere Evolution , 2000, Cell.

[81]  M. Hattori,et al.  The DNA sequence of human chromosome 21 , 2000, Nature.

[82]  W. Filipowicz,et al.  In Vitro Assembly of Human H/ACA Small Nucleolar RNPs Reveals Unique Features of U17 and Telomerase RNAs , 2000, Molecular and Cellular Biology.

[83]  L. Guarente,et al.  Nijmegen breakage syndrome disease protein and MRE11 at PML nuclear bodies and meiotic telomeres. , 2000, Cancer research.

[84]  L. Guarente,et al.  Sir2 links chromatin silencing, metabolism, and aging. , 2000, Genes & development.

[85]  Jiunn-Liang Chen,et al.  Secondary Structure of Vertebrate Telomerase RNA , 2000, Cell.

[86]  M. Benedict,et al.  Mosaic: a position-effect variegation eye-color mutant in the mosquito Anopheles gambiae. , 2000, The Journal of heredity.

[87]  B. van Steensel,et al.  Control of Human Telomere Length by TRF1 and TRF2 , 2000, Molecular and Cellular Biology.

[88]  M. A. Vega-Palas,et al.  Telomeric silencing of a natural subtelomeric gene , 2000, Molecular and General Genetics MGG.

[89]  R. Sternglanz,et al.  Identification of two RNA-binding proteins associated with human telomerase RNA. , 2000, Molecular biology of the cell.

[90]  L. Guarente,et al.  Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase , 2000, Nature.

[91]  M. D'Esposito,et al.  Differentially regulated and evolved genes in the fully sequenced Xq/Yq pseudoautosomal region. , 2000, Human molecular genetics.

[92]  Michel Labouesse,et al.  RNA interference: genetic wand and genetic watchdog , 2000, Nature Cell Biology.

[93]  S. R. Himes,et al.  Assays for transcriptional activity based on the luciferase reporter gene. , 2000, Methods in molecular biology.

[94]  K. Collins,et al.  A telomerase component is defective in the human disease dyskeratosis congenita , 1999, Nature.

[95]  Melanie E. Goward,et al.  The DNA sequence of human chromosome 22 , 1999, Nature.

[96]  John J. Wyrick,et al.  Chromosomal landscape of nucleosome-dependent gene expression and silencing in yeast , 1999, Nature.

[97]  V. Kickhoefer,et al.  Vaults and Telomerase Share a Common Subunit, TEP1* , 1999, The Journal of Biological Chemistry.

[98]  J. Campisi,et al.  TIN2, a new regulator of telomere length in human cells , 1999, Nature Genetics.

[99]  J. Wienberg,et al.  Defining the ancestral karyotype of all primates by multidirectional chromosome painting between tree shrews, lemurs and humans , 1999, Chromosoma.

[100]  Mark Groudine,et al.  A Functional Enhancer Suppresses Silencing of a Transgene and Prevents Its Localization Close to Centromeric Heterochromatin , 1999, Cell.

[101]  E. Blackburn,et al.  Ku is associated with the telomere in mammals. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[102]  D. Shore,et al.  Yeast Ku protein plays a direct role in telomeric silencing and counteracts inhibition by Rif proteins , 1999, Current Biology.

[103]  M. Shulman,et al.  Variegated Expression of the Endogenous Immunoglobulin Heavy-Chain Gene in the Absence of the Intronic Locus Control Region , 1999, Molecular and Cellular Biology.

[104]  J. Russo,et al.  Functional roles of chromosomes 11 and 17 in the transformation of human breast epithelial cells in vitro. , 1999, International journal of oncology.

[105]  K. Skorecki,et al.  Position effect of human telomeric repeats on replication timing. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[106]  T. Cech,et al.  Saccharomyces cerevisiae telomerase is an Sm small nuclear ribonucleoprotein particle , 1999, Nature.

[107]  J. Murray,et al.  DNA damage triggers disruption of telomeric silencing and Mec1p-dependent relocation of Sir3p , 1999, Current Biology.

[108]  S. Köhler,et al.  Trypanosoma brucei: improved detection of nuclear transcripts reveals a genomic position effect on nuclearly accumulating NEO RNAs visualized in stably transformed cells. , 1999, Experimental parasitology.

[109]  Robert A. Weinberg,et al.  Creation of human tumour cells with defined genetic elements , 1999, Nature.

[110]  S. Elgin,et al.  Silencing at Drosophila telomeres: nuclear organization and chromatin structure play critical roles , 1999, The EMBO journal.

[111]  J. Haber,et al.  Sir-Ku-itous Routes to Make Ends Meet , 1999, Cell.

[112]  Sophie G. Martin,et al.  Relocalization of Telomeric Ku and SIR Proteins in Response to DNA Strand Breaks in Yeast , 1999, Cell.

[113]  L. Guarente,et al.  MEC1-Dependent Redistribution of the Sir3 Silencing Protein from Telomeres to DNA Double-Strand Breaks , 1999, Cell.

[114]  C. Greider.  Telomeres Do D-Loop–T-Loop , 1999, Cell.

[115]  J. Griffith,et al.  Mammalian Telomeres End in a Large Duplex Loop , 1999, Cell.

[116]  G. Fourel,et al.  Cohabitation of insulators and silencing elements in yeast subtelomeric regions , 1999, The EMBO journal.

[117]  F. Pryde,et al.  Limitations of silencing at native yeast telomeres , 1999, The EMBO journal.

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

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

[120]  G. Morin,et al.  Functional requirement of p23 and Hsp90 in telomerase complexes. , 1999, Genes & development.

[121]  A. Fisher,et al.  Dynamic repositioning of genes in the nucleus of lymphocytes preparing for cell division. , 1999, Molecular cell.

[122]  Jeffrey B. Cheng,et al.  A Box H/ACA Small Nucleolar RNA-Like Domain at the Human Telomerase RNA 3′ End , 1999, Molecular and Cellular Biology.

[123]  K. Collins,et al.  Ciliate telomerase biochemistry. , 1999, Annual review of biochemistry.

[124]  J. Graves,et al.  The origin and evolution of the pseudoautosomal regions of human sex chromosomes. , 1998, Human molecular genetics.

[125]  Madhur Kumar,et al.  Antisense RNA: Function and Fate of Duplex RNA in Cells of Higher Eukaryotes , 1998, Microbiology and Molecular Biology Reviews.

[126]  T. Lange,et al.  Tankyrase, a poly(ADP-ribose) polymerase at human telomeres. , 1998, Science.

[127]  A. Scherf,et al.  Antigenic variation in malaria: in situ switching, relaxed and mutually exclusive transcription of var genes during intra‐erythrocytic development in Plasmodium falciparum , 1998, The EMBO journal.

[128]  H Kitano,et al.  Heterochromatin islands and their dynamic reorganization: a hypothesis for three distinctive features of cellular aging. , 1998, Experimental gerontology.

[129]  V. van Heyningen,et al.  Position effect in human genetic disease. , 1998, Human molecular genetics.

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

[131]  J. Boeke,et al.  Distribution of a limited Sir2 protein pool regulates the strength of yeast rDNA silencing and is modulated by Sir4p. , 1998, Genetics.

[132]  S. Gasser,et al.  Sif2p interacts with the Sir4p amino-terminal domain and antagonizes telomeric silencing in yeast , 1998, Current Biology.

[133]  S. Dupuis,et al.  Telomere elongation by hnRNP A1 and a derivative that interacts with telomeric repeats and telomerase , 1998, Nature Genetics.

[134]  T. Ley,et al.  Stochastic, stage-specific mechanisms account for the variegation of a human globin transgene. , 1998, Nucleic acids research.

[135]  Edward J. Louis,et al.  Mutation of yeast Ku genes disrupts the subnuclear organization of telomeres , 1998, Current Biology.

[136]  M. Grunstein.  Yeast Heterochromatin: Regulation of Its Assembly and Inheritance by Histones , 1998, Cell.

[137]  R. DePinho,et al.  Essential role of mouse telomerase in highly proliferative organs , 1998, Nature.

[138]  Robin C. Allshire,et al.  Defective meiosis in telomere-silencing mutants of Schizosaccharomyces pombe , 1998, Nature.

[139]  S. Jackson,et al.  Components of the Ku‐dependent non‐homologous end‐joining pathway are involved in telomeric length maintenance and telomeric silencing , 1998, The EMBO journal.

[140]  P. Borst,et al.  beta-D-glucosyl-hydroxymethyluracil is a conserved DNA modification in kinetoplastid protozoans and is abundant in their telomeres. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[141]  P. Borst,et al.  Changing the end: antigenic variation orchestrated at the telomeres of African trypanosomes. , 1998, Trends in microbiology.

[142]  A. Ciccodicola,et al.  A novel pseudoautosomal gene encoding a putative GTP-binding protein resides in the vicinity of the Xp/Yp telomere. , 1998, Human molecular genetics.

[143]  A. Fire,et al.  Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans , 1998, Nature.

[144]  C. Harley,et al.  Extension of life-span by introduction of telomerase into normal human cells. , 1998, Science.

[145]  R. Ward,et al.  Short telomeres on human chromosome 17p. , 1998 .

[146]  B. Trask,et al.  Members of the olfactory receptor gene family are contained in large blocks of DNA duplicated polymorphically near the ends of human chromosomes. , 1998, Human molecular genetics.

[147]  L. Guarente,et al.  Extrachromosomal rDNA Circles— A Cause of Aging in Yeast , 1997, Cell.

[148]  Matthias Merkenschlager,et al.  Association of Transcriptionally Silent Genes with Ikaros Complexes at Centromeric Heterochromatin , 1997, Cell.

[149]  T. Hunter,et al.  Characterization and cell cycle regulation of the related human telomeric proteins Pin2 and TRF1 suggest a role in mitosis. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[150]  M. Bass,et al.  Human telomerase contains evolutionarily conserved catalytic and structural subunits. , 1997, Genes & development.

[151]  J. Shay,et al.  Normal human chromosomes have long G-rich telomeric overhangs at one end. , 1997, Genes & development.

[152]  R. Reddel,et al.  Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines , 1997, Nature Medicine.

[153]  D. Broccoli,et al.  Human telomeres contain two distinct Myb–related proteins, TRF1 and TRF2 , 1997, Nature Genetics.

[154]  C B Harley,et al.  Telomerase catalytic subunit homologs from fission yeast and human. , 1997, Science.

[155]  B. Zhang,et al.  Constitutive mutations of the Saccharomyces cerevisiae MAL-activator genes MAL23, MAL43, MAL63, and mal64. , 1997, Genetics.

[156]  H. Biessmann,et al.  Telomere maintenance without telomerase. , 1997, Chromosoma.

[157]  B. Villeponteau.  The heterochromatin loss model of aging , 1997, Experimental Gerontology.

[158]  Wei Han,et al.  Telomerase regulation, cell cycle, and telomere stability in primitive hematopoietic cells. , 1997, Blood.

[159]  M. Aigle,et al.  Incidence of SUC-RTM telomeric repeated genes in brewing and wild wine strains of Saccharomyces , 1997, Current Genetics.

[160]  Mala Murthy,et al.  Redistribution of Silencing Proteins from Telomeres to the Nucleolus Is Associated with Extension of Life Span in S. cerevisiae , 1997, Cell.

[161]  R. Reddel,et al.  Telomere dynamics and telomerase activity in in vitro immortalised human cells. , 1997, European journal of cancer.

[162]  J. Shay,et al.  A survey of telomerase activity in human cancer. , 1997, European journal of cancer.

[163]  A. Matsuura,et al.  TLP1: A Gene Encoding a Protein Component of Mammalian Telomerase Is a Novel Member of WD Repeats Family , 1997, Cell.

[164]  J. Langmore,et al.  Long G Tails at Both Ends of Human Chromosomes Suggest a C Strand Degradation Mechanism for Telomere Shortening , 1997, Cell.

[165]  M. A. Vega-Palas,et al.  Telomeric transcriptional silencing in a natural context , 1997, Nature Genetics.

[166]  J. Flint,et al.  The relationship between chromosome structure and function at a human telomeric region , 1997, Nature Genetics.

[167]  E. Nimmo,et al.  Regulation of telomere length and function by a Myb-domain protein in fission yeast , 1997, Nature.

[168]  Lea Harrington,et al.  A Mammalian Telomerase-Associated Protein , 1997, Science.

[169]  D. Shore,et al.  A Protein-Counting Mechanism for Telomere Length Regulation in Yeast , 1997, Science.

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

[171]  D. Shore,et al.  Rap1p and telomere length regulation in yeast. , 1997, Ciba Foundation symposium.

[172]  Gregg B. Morin,et al.  Reconstitution of human telomerase with the template RNA component hTR and the catalytic protein subunit hTRT , 1997, Nature Genetics.

[173]  D. Shore,et al.  Evidence that the transcriptional regulators SIN3 and RPD3, and a novel gene (SDS3) with similar functions, are involved in transcriptional silencing in S. cerevisiae. , 1996, Genetics.

[174]  V A Zakian,et al.  Structure, function, and replication of Saccharomyces cerevisiae telomeres. , 1996, Annual review of genetics.

[175]  E. Whitelaw,et al.  The vagaries of variegating transgenes. , 1996, BioEssays : news and reviews in molecular, cellular and developmental biology.

[176]  J. Murnane,et al.  Effect of telomere length on telomeric gene expression. , 1996, Nucleic acids research.

[177]  H. Scherthan,et al.  The clustering of telomeres and colocalization with Rap1, Sir3, and Sir4 proteins in wild-type Saccharomyces cerevisiae , 1996, The Journal of cell biology.

[178]  A. Villeneuve,et al.  Telomeric repeats (TTAGGC)n are sufficient for chromosome capping function in Caenorhabditis elegans. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[179]  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.

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

[181]  D. Shore,et al.  Silencing of genes at nontelomeric sites in yeast is controlled by sequestration of silencing factors at telomeres by Rap 1 protein. , 1996, Genes & development.

[182]  D. Agard,et al.  Perturbation of Nuclear Architecture by Long-Distance Chromosome Interactions , 1996, Cell.

[183]  David Levens,et al.  Heterogeneous nuclear ribonucleoprotein K is a transcription factor , 1996, Molecular and cellular biology.

[184]  J. Shay,et al.  Experimental elongation of telomeres extends the lifespan of immortal x normal cell hybrids. , 1996, The EMBO journal.

[185]  D. Kioussis,et al.  Locus Control Region Function and Heterochromatin-Induced Position Effect Variegation , 1996, Science.

[186]  S. Jazwinski,et al.  Effect of replicative age on transcriptional silencing near telomeres in Saccharomyces cerevisiae. , 1996, Biochemical and biophysical research communications.

[187]  D. Scalzo,et al.  Transcriptional enhancers act in cis to suppress position-effect variegation. , 1996, Genes & development.

[188]  J. Shay,et al.  Telomerase activity in human germline and embryonic tissues and cells. , 1996, Developmental genetics.

[189]  R. Needleman,et al.  Removal of Mig1p binding site converts a MAL63 constitutive mutant derived by interchromosomal gene conversion to glucose insensitivity. , 1996, Genetics.

[190]  H. Erdjument-Bromage,et al.  A Human Telomeric Protein , 1995, Science.

[191]  E. Louis,et al.  The chromosome ends of Saccharomyces cerevisiae , 1995, Yeast.

[192]  G. Cross,et al.  A developmentally regulated position effect at a telomeric locus in Trypanosoma brucei , 1995, Cell.

[193]  M. Oshimura,et al.  Restoration of the Cellular Senescence Program and Repression of Telomerase by Human Chromosome 3 , 1995, Japanese journal of cancer research : Gann.

[194]  D. Broccoli,et al.  Telomerase activity in normal and malignant hematopoietic cells. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[195]  M. Gossen,et al.  Co-regulation of two gene activities by tetracycline via a bidirectional promoter. , 1995, Nucleic acids research.

[196]  J. Vermeesch,et al.  The IL-9 receptor gene (IL9R): genomic structure, chromosomal localization in the pseudoautosomal region of the long arm of the sex chromosomes, and identification of IL9R pseudogenes at 9qter, 10pter, 16pter, and 18pter. , 1995, Genomics.

[197]  et al.,et al.  The RNA component of human telomerase , 1995, Science.

[198]  M. Groudine,et al.  Enhancers increase the probability but not the level of gene expression. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[199]  D. Shore,et al.  Disturbance of normal cell cycle progression enhances the establishment of transcriptional silencing in Saccharomyces cerevisiae , 1995, Molecular and cellular biology.

[200]  M. Gossen,et al.  Transcriptional activation by tetracyclines in mammalian cells. , 1995, Science.

[201]  S. Elgin,et al.  Position effect variegation in Drosophila is associated with an altered chromatin structure. , 1995, Genes & development.

[202]  Andreas Hecht,et al.  Histone H3 and H4 N-termini interact with SIR3 and SIR4 proteins: A molecular model for the formation of heterochromatin in yeast , 1995, Cell.

[203]  D. Shore,et al.  Action of a RAP1 carboxy-terminal silencing domain reveals an underlying competition between HMR and telomeres in yeast. , 1995, Genes & development.

[204]  H. Biessmann,et al.  The unusual telomeres of Drosophila. , 1995, Trends in genetics : TIG.

[205]  M. Kalos,et al.  Position-independent transgene expression mediated by boundary elements from the apolipoprotein B chromatin domain , 1995, Molecular and cellular biology.

[206]  B. Wakimoto,et al.  Heterochromatin and gene expression in Drosophila. , 1995, Annual review of genetics.

[207]  V. Zakian,et al.  Extra telomeres, but not internal tracts of telomeric DNA, reduce transcriptional repression at Saccharomyces telomeres. , 1995, Genetics.

[208]  C B Harley,et al.  Specific association of human telomerase activity with immortal cells and cancer. , 1994, Science.

[209]  J. Murnane,et al.  Telomere dynamics in an immortal human cell line. , 1994, The EMBO journal.

[210]  J. Yanowitz,et al.  Stringent sequence requirements for the formation of human telomeres. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[211]  J E Hewitt,et al.  Analysis of the tandem repeat locus D4Z4 associated with facioscapulohumeral muscular dystrophy. , 1994, Human molecular genetics.

[212]  R. Allshire,et al.  Telomere‐associated chromosome breakage in fission yeast results in variegated expression of adjacent genes. , 1994, The EMBO journal.

[213]  R. W. Jones,et al.  Genome structure and evolution in Drosophila: applications of the framework P1 map. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[214]  J. Stavenhagen,et al.  Internal tracts of telomeric DNA act as silencers in Saccharomyces cerevisiae. , 1994, Genes & development.

[215]  O. Aparicio,et al.  Overcoming telomeric silencing: a trans-activator competes to establish gene expression in a cell cycle-dependent way. , 1994, Genes & development.

[216]  G. Karpen,et al.  Position-effect variegation and the new biology of heterochromatin. , 1994, Current opinion in genetics & development.

[217]  D. Broccoli,et al.  Sandwiching of a gene within 12 kb of a functional telomere and alpha satellite does not result in silencing. , 1994, Human molecular genetics.

[218]  M. Crow,et al.  Altered transcriptional regulation of human interstitial collagenase in cultured skin fibroblasts from older donors , 1994, Experimental Gerontology.

[219]  R. Allshire,et al.  Position effect variegation at fission yeast centromeres , 1994, Cell.

[220]  G. Butcher,et al.  A mammalian homologue of Drosophila heterochromatin protein 1 (HP1) is a component of constitutive heterochromatin. , 1994, Cytogenetics and cell genetics.

[221]  R. Levis,et al.  Transposons in place of telomeric repeats at a Drosophila telomere , 1993, Cell.

[222]  P. Borst,et al.  β-d-glucosyl-hydroxymethyluracil: A novel modified base present in the DNA of the parasitic protozoan T. brucei , 1993, Cell.

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

[224]  A. Lustig,et al.  RAP1 and telomere structure regulate telomere position effects in Saccharomyces cerevisiae. , 1993, Genes & development.

[225]  R. Moyzis,et al.  Physical analysis of the terminal 240 kb of DNA from human chromosome 7q. , 1993, Genomics.

[226]  Sanjay K. Chhablani,et al.  Silent domains are assembled continuously from the telomere and are defined by promoter distance and strength, and by SIR3 dosage. , 1993, Genes & development.

[227]  G. Dreyfuss,et al.  Nuclear proteins that bind the pre-mRNA 3' splice site sequence r(UUAG/G) and the human telomeric DNA sequence d(TTAGGG)n , 1993, Molecular and cellular biology.

[228]  I. Makunin,et al.  Observations on the induction of position effect variegation of euchromatic genes in Drosophila melanogaster. , 1993, Genetics.

[229]  Michael A. Barnett,et al.  Telomere directed fragmentation of mammalian chromosomes , 1993, Nucleic Acids Res..

[230]  H. Cooke,et al.  hnRNP A2/B1 binds specifically to single stranded vertebrate telomeric repeat TTAGGGn. , 1992, Nucleic acids research.

[231]  P. Goodfellow,et al.  Telomere–associated chromosome fragmentation: applications in genome manipulation and analysis , 1992, Nature Genetics.

[232]  A. Lustig,et al.  C-terminal truncation of RAP1 results in the deregulation of telomere size, stability, and function in Saccharomyces cerevisiae , 1992, Molecular and cellular biology.

[233]  R. Pignolo,et al.  Differential gene expression between young and senescent, quiescent WI-38 cells , 1992, Mechanisms of Ageing and Development.

[234]  M. Gossen,et al.  Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[235]  J. Shay,et al.  Telomere positional effects and the regulation of cellular senescence. , 1992, Trends in genetics : TIG.

[236]  S. Henikoff,et al.  Position effect and related phenomena. , 1992, Current opinion in genetics & development.

[237]  P. Goodfellow,et al.  Functional reintroduction of human telomeres into mammalian cells. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[238]  Paul Schedl,et al.  A position-effect assay for boundaries of higher order chromosomal domains , 1991, Cell.

[239]  W. Brown,et al.  Stable length polymorphism of up to 260 kb at the tip of the short arm of human chromosome 16 , 1991, Cell.

[240]  W. Brown,et al.  Structure and polymorphism of human telomere-associated DNA , 1990, Cell.

[241]  C. Harley,et al.  Telomeres shorten during ageing of human fibroblasts , 1990, Nature.

[242]  J. Bishop,et al.  Expression of a foreign gene in a line of transgenic mice is modulated by a chromosomal position effect , 1990, Molecular and cellular biology.

[243]  R. Myers,et al.  Structure and variability of human chromosome ends , 1990, Molecular and cellular biology.

[244]  A. Miller.  Retrovirus packaging cells. , 1990, Human gene therapy.

[245]  G. Morin.  The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats , 1989, Cell.

[246]  M. Olson,et al.  Cloning human telomeric DNA fragments into Saccharomyces cerevisiae using a yeast-artificial-chromosome vector. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[247]  D. Mann,et al.  Regulation of collagenase and collagenase mRNA production in early‐ and late‐passage human diploid fibroblasts , 1989, Journal of cellular physiology.

[248]  L. S. Cram,et al.  A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[249]  L. Corcoran,et al.  Homologous recombination within subtelomeric repeat sequences generates chromosome size polymorphisms in P. falciparum , 1988, Cell.

[250]  J. Hegemann,et al.  Mutational analysis of centromere DNA from chromosome VI of Saccharomyces cerevisiae. , 1988, Molecular and cellular biology.

[251]  Carol W. Greider,et al.  The telomere terminal transferase of tetrahymena is a ribonucleoprotein enzyme with two kinds of primer specificity , 1987, Cell.

[252]  G. Natsoulis,et al.  5-Fluoroorotic acid as a selective agent in yeast molecular genetics. , 1987, Methods in enzymology.

[253]  K. Butner,et al.  Modulation of tk expression in mouse pericentromeric heterochromatin , 1986, Molecular and cellular biology.

[254]  Paul Russell,et al.  Schizosaccharomyces pombe and saccharomyces cerevisiae: A look at yeasts divided , 1986, Cell.

[255]  J. Rine,et al.  A position effect on the expression of a tRNA gene mediated by the SIR genes in Saccharomyces cerevisiae , 1986, Molecular and cellular biology.

[256]  H. Cooke,et al.  Variability at the telomeres of the human X/Y pseudoautosomal region. , 1986, Cold Spring Harbor symposia on quantitative biology.

[257]  G. Rubin,et al.  Effects of genomic position on the expression of transduced copies of the white gene of Drosophila. , 1985, Science.

[258]  W. Gehring,et al.  Functional analysis of the white+ gene of Drosophila by P‐factor‐mediated transformation , 1984, The EMBO journal.

[259]  C. Hobbs,et al.  A structural basis for variegating position effects , 1984, Cell.

[260]  G. Rubin,et al.  Transformation of white locus DNA in Drosophila: Dosage compensation, zeste interaction, and position effects , 1984, Cell.

[261]  M. Pardue,et al.  Telomere regions in drosophila share complex DNA sequences with pericentric heterochromatin , 1983, Cell.

[262]  S. Liming,et al.  Comparative cytogenetic studies on the red muntjac, Chinese muntjac, and their F1 hybrids. , 1980, Cytogenetics and cell genetics.

[263]  E. Blackburn,et al.  A tandemly repeated sequence at the termini of the extrachromosomal ribosomal RNA genes in Tetrahymena. , 1978, Journal of molecular biology.

[264]  H. L. Carson,et al.  The Genetics and Biology of Drosophila , 1976, Heredity.

[265]  B. Cattanach.  Position effect variegation in the mouse. , 1974, Genetical research.

[266]  A M Olovnikov,et al.  A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon. , 1973, Journal of theoretical biology.

[267]  J. D. Watson.  Origin of Concatemeric T7DNA , 1972 .

[268]  T. Thelen,et al.  Multiple abnormalities due to possible genetic inactivation in an X-autosome translocation. , 1971, American journal of human genetics.

[269]  Olovnikov Am.  Principle of marginotomy in template synthesis of polynucleotides , 1971 .

[270]  I. Hartmann-Goldstein.  On the relationship between heterochromatization and variegation in Drosophila, with special reference to temperature-sensitive periods. , 1967, Genetical research.

[271]  L. B. Russell,et al.  The use of x-autosome translocations in locating the x-chromosome inactivation center. Abstr. , 1965 .

[272]  L. B. Russell,et al.  Variegated-type position effects in the mouse. , 1961, Genetics.

[273]  H. Roman.  Studies of gene mutation in Saccharomyces. , 1956, Cold Spring Harbor symposia on quantitative biology.

[274]  F. Crick,et al.  Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid , 1953, Nature.

[275]  E. Lewis.  The phenomenon of position effect. , 1950, Advances in genetics.

[276]  B. Mcclintock,et al.  The Stability of Broken Ends of Chromosomes in Zea Mays. , 1941, Genetics.

[277]  M. Demerec.  The nature of changes in the white-notch region of the X-chromosome of Drosophila melanogaster , 1941 .

[278]  M. Demerec.  Genetic Behavior of Euchromatic Segments Inserted into Heterochromatin. , 1940, Genetics.

[279]  M. Demerec,et al.  Mottled White 258-18 of Drosophila Melanogaster. , 1937, Genetics.

[280]  J. Schultz.  Variegation in Drosophila and the Inert Chromosome Regions. , 1936, Proceedings of the National Academy of Sciences of the United States of America.

[281]  M. Demerec.  Miniature-alpha-A Second Frequently Mutating Character in Drosophila Virilis. , 1926, Proceedings of the National Academy of Sciences of the United States of America.

[282]  A. Sturtevant.  The Effects of Unequal Crossing over at the Bar Locus in Drosophila. , 1925, Genetics.