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Repeat-induced gene silencing in mammals
Abstract
In both plants and Drosophila melanogaster, expression from a transgenic locus may be silenced when repeated transgene copies are arranged as a concatameric array. This repeat-induced gene silencing is frequently manifested as a decrease in the proportion of cells that express the transgene, resulting in a variegated pattern of expression. There is also some indication that, in transgenic mammals, the number of transgene copies within an array can exert a repressive influence on expression, with several mouse studies reporting a decrease in the level of expression per copy as copy number increases. However, because these studies compare different sites of transgene integration as well as arrays with different numbers of copies, the expression levels observed may be subject to varying position effects as well as the influence of the multicopy array. Here we describe use of the lox/Cre system of site-specific recombination to generate transgenic mouse lines in which different numbers of a transgene are present at the same chromosomal location, thereby eliminating the contribution of position effects and allowing analysis of the effect of copy number alone on transgene silencing. Reduction in copy number results in a marked increase in expression of the transgene and is accompanied by decreased chromatin compaction and decreased methylation at the transgene locus. These findings establish that the presence of multiple homologous copies of a transgene within a concatameric array can have a repressive effect upon gene expression in mammalian systems.
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“This site of integration is neither centromeric nor telomeric, and so presumably the silencing is related to the multicopy nature of the transgene array [13,14].”
From A genome-wide screen for modifiers of transgene variegation identifies genes with critical roles in development (2008) · cites this paper as [13]
In the citing paper
“transgene silencing,4”
From Adeno‐associated virus gene repair corrects a mouse model of hereditary tyrosinemia in vivo†‡ (2010) · cites this paper as [4]
Citations
Cites
Position-independent, high-level expression of the human β-globin gene in transgenic mice
Grosveld, F. G., van Assendelft, G. B., Greaves, D. R., & Kollias, G. A. (1987) · Cell · doi:10.1016/0092-8674(87)90584-8 · Cited by 1,908
GERM-LINE TRANSFORMATION OF MICE
Palmiter, R. D., & Brinster, R. L. (1986) · Annual Review of Genetics · doi:10.1146/annurev.ge.20.120186.002341 · Cited by 1,157
Efficient in vivo manipulation of mouse genomic sequences at the zygote stage.
Lakso, M., Pichel, J. G., Gorman, J. R., Sauer, B., Okamoto, Y., Lee, E., Alt, F. W., & Westphal, H. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.12.5860 · Cited by 1,125
Reversible methylation and inactivation of marker genes in sequentially transformed tobacco plants
Matzke, M. A., Primig, M., Trnovsky, J., & Matzke, A. J. M. (1989) · The EMBO Journal · doi:10.1002/j.1460-2075.1989.tb03421.x · Cited by 545
Expansions of transgene repeats cause heterochromatin formation and gene silencing in Drosophila
Dorer, D. R. (1994) · Cell · doi:10.1016/0092-8674(94)90439-1 · Cited by 504
The basics of basal transcription by RNA polymerase II
Buratowski, S. (1994) · Cell · doi:10.1016/0092-8674(94)90226-7 · Cited by 410
A major positive regulatory region located far upstream of the human alpha-globin gene locus.Preprint
Higgs, D. R., Wood, W. G., Jarman, A. P., Sharpe, J. A., Lida, J., Pretorius, I., & Ayyub, H. (1990) · Genes & Development · doi:10.1101/gad.4.9.1588 · Cited by 335
Suppression of beta‐1,3‐glucanase transgene expression in homozygous plants.
de Carvalho‐Niebel, F., Gheysen, G., Kushnir, S., MONTAGU, M. V., Inzé, D., & Castresana, C. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05324.x · Cited by 304
Araki, K., Araki, M., Miyazaki, J., & VASSALLI, P. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.1.160 · Cited by 284
Linne, F., Heidmann, I., Saedler, H., & Meyer, P. (1990) · Molecular and General Genetics MGG · doi:10.1007/bf00633837 · Cited by 281
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Bird, A. (2002) · Genes & Development · doi:10.1101/gad.947102 · Cited by 7,124
“The most suggestive evidence in mammals concerns manipulation of transgene copy number at a single locus in the mouse genome using cre-lox technology (Garrick et al. 1998).”
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Hong, S., Beja-Glasser, V. F., Nfonoyim, B. M., Frouin, A., Li, S., Ramakrishnan, S., Merry, K. M., Shi, Q., Rosenthal, A., Barres, B. A., et al. (2016) · Science · doi:10.1126/science.aad8373 · Cited by 3,343
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Feng, G., Mellor, R. H., Bernstein, M., Keller-Peck, C., Nguyen, Q. T., Wallace, M., Nerbonne, J. M., Lichtman, J. W., & Sanes, J. R. (2000) · Neuron · doi:10.1016/s0896-6273(00)00084-2 · Cited by 3,042
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Livet, J., Weissman, T. A., Kang, H., Draft, R. W., Lu, J., Bennis, R. A., Sanes, J. R., & Lichtman, J. W. (2007) · Nature · doi:10.1038/nature06293 · Cited by 1,876
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Bird, A. P., & Wolffe, A. P. (1999) · Cell · doi:10.1016/s0092-8674(00)81532-9 · Cited by 1,858
Cytokines in Atherosclerosis: Pathogenic and Regulatory Pathways
Tedgui, A., & Mallat, Z. (2006) · Physiological Reviews · doi:10.1152/physrev.00024.2005 · Cited by 1,751
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Ehrlich, M. (2002) · Oncogene · doi:10.1038/sj.onc.1205651 · Cited by 1,563
“DNA methylation has been linked to histone hypoacetylation and heterochromatinization (Garrick et al., 1998; Nguyen et al., 2001b).”
BackgroundYokota, T., Oritani, K., Takahashi, I., Ishikawa, J., Matsuyama, A., Ouchi, N., Kihara, S., Funahashi, T., Tenner, A. J., Tomiyama, Y., et al. (2000) · Blood · doi:10.1182/blood.v96.5.1723 · Cited by 1,294
Epigenetics: Regulation Through Repression
Wolffe, A. P., & Matzke, M. A. (1999) · Science · doi:10.1126/science.286.5439.481 · Cited by 1,261
Ogden, C. A., deCathelineau, A. M., Hoffmann, P. R., Bratton, D. L., Ghebrehiwet, B., Fadok, V. A., & Henson, P. M. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.6.781 · Cited by 1,148
Robertson, K. D., Ait-Si-Ali, S., Yokochi, T., Wade, P. A., Jones, P. L., & Wolffe, A. P. (2000) · Nature Genetics · doi:10.1038/77124 · Cited by 942
“Mammalian DNA methyltransferases show little sequence specificity in vitro , yet methylation can be targeted in vivo within chromosomes to repetitive element”
BackgroundPathogenesis of systemic lupus erythematosus
Mok, C. C., & Lau, C. S. (2003) · Journal of Clinical Pathology · doi:10.1136/jcp.56.7.481 · Cited by 947
Conditional control of gene expression in the mouse
Lewandoski, M. (2001) · Nature reviews genetics · doi:10.1038/35093537 · Cited by 442
Interspersed repeats and other mementos of transposable elements in mammalian genomes
Smit, A. F. (1999) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(99)00031-3 · Cited by 949
Taylor, P. R., Carugati, A., Fadok, V. A., Cook, H. T., Andrews, M., Carroll, M. C., Savill, J., Henson, P. M., Botto, M., & Walport, M. J. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.3.359 · Cited by 724
Complement-dependent Clearance of Apoptotic Cells by Human Macrophages
Mevorach, D., Mascarenhas, J., Gershov, D., & Elkon, K. (1998) · Journal of Experimental Medicine · doi:10.1084/jem.188.12.2313 · Cited by 776
Lee, C. S., Bishop, E. S., Zhang, R., Yu, X., Farina, E. M., Yan, S., Zhao, C., Zeng, Z., Shu, Y., Wu, X., et al. (2017) · Genes & Diseases · doi:10.1016/j.gendis.2017.04.001 · Cited by 691
Understanding transgenerational epigenetic inheritance via the gametes in mammals
Daxinger, L., & Whitelaw, E. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3188 · Cited by 728
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BackgroundSelf-citationGershov, D., Kim, S., Brot, N., & Elkon, K. B. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.9.1353 · Cited by 695
Uchida, J., Hamaguchi, Y., Oliver, J. A., Ravetch, J. V., Poe, J. C., Haas, K. M., & Tedder, T. F. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20040119 · Cited by 653
Cohen, P. L., Caricchio, R., Abraham, V., Camenisch, T. D., Jennette, J. C., Roubey, R. A. S., Earp, H. S., Matsushima, G. K., & Reap, E. A. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20012094 · Cited by 637
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Gaetano, N. D., Cittera, E., Nota, R., Vecchi, A., Grieco, V., Scanziani, E., Botto, M., Introna, M., & Golay, J. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.3.1581 · Cited by 574
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Elliott, M. R., & Ravichandran, K. S. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.201004096 · Cited by 568
Regulation of B Lymphocyte Responses to Foreign and Self-Antigens by the CD19/CD21 Complex
Fearon, D. T., Carroll, M. C., & Carroll, M. C. (2000) · Annual Review of Immunology · doi:10.1146/annurev.immunol.18.1.393 · Cited by 529
I-SceI meganuclease mediates highly efficient transgenesis in fish
Thermes, V., Grabher, C., Ristoratore, F., Bourrat, F., Choulika, A., Wittbrodt, J., & Joly, J. (2002) · Mechanisms of Development · doi:10.1016/s0925-4773(02)00218-6 · Cited by 522
Uccellini, M. B., Broughton, C., Mackay, F., Akira, S., Marshak‐Rothstein, A., & Rifkin, I. R. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20031942 · Cited by 528
Vandivier, R. W., Ogden, C. A., Fadok, V. A., Hoffmann, P. R., Brown, K. K., Botto, M., Walport, M. J., Fisher, J. H., Henson, P. M., & Greene, K. E. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.7.3978 · Cited by 517
Vollmer, J., Tluk, S., Schmitz, C., Hamm, S., Jurk, M., Forsbach, A., Akira, S., Kelly, K. M., Reeves, W. H., Bauer, S., et al. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20051696 · Cited by 515
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Casciola-Rosen, L. A., Andrade, F., Ulanet, D., Wong, W. B., & Rosen, A. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.190.6.815 · Cited by 492
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“Repeated sequences can attract de novo methylation; a transgene array of tandem repeats became methylated in transgenic mice, but methylation was lost when the repeat array was reduced to a single unit [19].”
BackgroundLuche, H., Weber, O., Nageswara Rao, T., Blum, C., & Fehling, H. J. (2007) · European Journal of Immunology · doi:10.1002/eji.200636745 · Cited by 482
Timescales of Genetic and Epigenetic Inheritance
Rando, O. J., & Verstrepen, K. J. (2007) · Cell · doi:10.1016/j.cell.2007.01.023 · Cited by 472
“A second system in mammals increases mutation rates over parasitic DNA elements such as transposons ( Garrick et al., 1998 ).”
Prominent neurodegeneration and increased plaque formation in complement-inhibited Alzheimer's mice
Wyss-Coray, T., Yan, F., Lin, A. H.-T., Lambris, J. D., Alexander, J. J., Quigg, R. J., & Masliah, E. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.162350199 · Cited by 446
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Farrera, C., & Fadeel, B. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1300436 · Cited by 456
A Dramatic Increase of C1q Protein in the CNS during Normal Aging
Stephan, A. H., Madison, D. V., Mateos, J. M., Fraser, D. A., Lovelett, E. A., Coutellier, L., Kim, L., Tsai, H.-H., Huang, E. J., Rowitch, D. H., et al. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.1333-13.2013 · Cited by 423
Seitz, H., Camenisch, T. D., Lemke, G., Earp, H. S., & Matsushima, G. K. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.9.5635 · Cited by 403
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Large multiallelic copy number variations in humans
Handsaker, R. E., Doren, V. V., Berman, J. R., Genovese, G., Kashin, S., Boettger, L. M., & McCarroll, S. A. (2015) · Nature Genetics · doi:10.1038/ng.3200 · Cited by 388
Pigs expressing salivary phytase produce low-phosphorus manure
Golovan, S. P., Meidinger, R. G., Ajakaiye, A., Cottrill, M., Wiederkehr, M. Z., Barney, D. J., Plante, C., Pollard, J. W., Fan, M. Z., Hayes, M. A., et al. (2001) · Nature Biotechnology · doi:10.1038/90788 · Cited by 387
“Excluding sampling difficulties, the variation in salivary phytase activities may have arisen from random repeat-induced silencin”
Nuclear Aggregation of Olfactory Receptor Genes Governs Their Monogenic Expression
Clowney, E. J., LeGros, M., Mosley, C., Clowney, F., Markenscoff-Papadimitriou, E., Myllys, M., Barnea, G., Larabell, C. A., & Lomvardas, S. (2012) · Cell · doi:10.1016/j.cell.2012.09.043 · Cited by 370
“also carries H3K9me3 and H4K20me3 (data not shown), but unlike the endogenous ORs, its heterochromatization is not OSN specific and is probably caused by its multicopy (16 tandem copies) insertion (Garrick et al., 1998).”
BackgroundBrown, J., Hussell, T., Gilliland, S. M., Holden, D. W., Paton, J. C., Ehrenstein, M. R., Walport, M. J., & Botto, M. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.012669199 · Cited by 366
Accelerated development of IgG autoantibodies and autoimmune disease in the absence of secreted IgM
Boes, M. L., Schmidt, T., Linkemann, K., Beaudette-Zlatanova, B. C., Marshak‐Rothstein, A., & Chen, J. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.3.1184 · Cited by 370
Absence of C1q Leads to Less Neuropathology in Transgenic Mouse Models of Alzheimer's Disease
Fonseca, M. I., Zhou, J., Botto, M., & Tenner, A. J. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.0901-04.2004 · Cited by 345
Vooijs, M., Jonkers, J., & Berns, A. J. M. (2001) · EMBO Reports · doi:10.1093/embo-reports/kve064 · Cited by 354
“However, the random integration of transgenes into the mouse genome often results in mosaic gene expression (Garrick et al., 1998; Henikoff, 1998) and offers little control over the level of gene-expression obtained.”
BackgroundGene transfer into genomes of human cells by the sleeping beauty transposon system
Geurts, A. M., Yang, Y., Clark, K. J., Liu, G., Cui, Z., Dupuy, A. J., Bell, J. B., Largaespada, D. A., & Hackett, P. B. (2003) · Molecular Therapy · doi:10.1016/s1525-0016(03)00099-6 · Cited by 357
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BackgroundGabriëls, J., Beckers, M. C., Ding, H., Vriese, A. S. D., Plaisance, S., van der Maarel, S. M., Padberg, G. W., Frants, R. R., Hewitt, J., Collen, D., et al. (1999) · Gene · doi:10.1016/s0378-1119(99)00267-x · Cited by 352
Bystander apoptosis triggers dendritic cell maturation and antigen-presenting function.
Rovere, P. Q., Vallinoto, C., Bondanza, A., Crosti, M., Rescigno, M., Ricciardi‐Castagnoli, P., Rugarli, C., & Manfredi, A. A. (1998) · PubMed · Cited by 352
Nathwani, A. C., Rosales, C., McIntosh, J., Rastegarlari, G., Nathwani, D., Raj, D., Nawathe, S., Waddington, S. N., Bronson, R., Jackson, S., et al. (2011) · Molecular Therapy · doi:10.1038/mt.2010.274 · Cited by 345
Apoptotic Cells with Oxidation-specific Epitopes Are Immunogenic and Proinflammatory
Chang, M.-K., Binder, C. J., Miller, Y. I., Subbanagounder, G., Silverman, G. J., Berliner, J. A., & Witztum, J. L. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20031763 · Cited by 337
A human B cell methylome at 100−base pair resolution
Rauch, T. A., Wu, X., Zhong, X., Riggs, A. D., & Pfeifer, G. P. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812399106 · Cited by 338
Silencing of Retrotransposons in Arabidopsis and Reactivation by the ddm1 Mutation
Hirochika, H., Okamoto, H. H., & Kakutani, T. (2000) · The Plant Cell · doi:10.1105/tpc.12.3.357 · Cited by 327
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Mutskov, V. J., & Felsenfeld, G. (2003) · The EMBO Journal · doi:10.1038/sj.emboj.7600013 · Cited by 296
“Copy number reduction in transgenic mouse lines caused a marked increase in expression of the transgenes and less compaction of the chromatin at the transgene locus ( Garrick et al, 1998 ).”
BackgroundMitchell, S., Thomas, G., Harvey, K., Cottell, D., Reville, K., Berlasconi, G., Petasis, N. A., Erwig, L., Rees, A. J., Savill, J., et al. (2002) · Journal of the American Society of Nephrology · doi:10.1097/01.asn.0000032417.73640.72 · Cited by 287
Schrem, H., Klempnauer, J., & Borlak, J. (2002) · Pharmacological Reviews · doi:10.1124/pr.54.1.129 · Cited by 283
“Experiments using the lox/ Cre system of site-specific recombination to generate transgenic mouse lines showed that the reduction in copy number results in a methylation at the transgene locus (Garrick et al., 1998).”
BackgroundMethodInfluentialKim, S. J., Gershov, D., Ma, X., Brot, N., & Elkon, K. B. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20020542 · Cited by 282
Stam, M. E., Belele, C. L., Dorweiler, J. E., & Chandler, V. L. (2002) · Genes & Development · doi:10.1101/gad.1006702 · Cited by 278
“2000; Vaucheret and Fagard 2001) and animals (Garrick et al. 1998; Henikoff 1998).”
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Roumenina, L. T., Daugan, M. V., Noé, R., Petitprez, F., Vano, Y. A., Sánchez-Salas, R., Becht, É., Meilleroux, J., Clec'h, B. L., Giraldo, N. A., et al. (2019) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-18-0891 · Cited by 280
Asano, K., Miwa, M., Miwa, K., Hanayama, R., Nagase, H., Nagata, S., & Tanaka, M. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20040342 · Cited by 268
Conservation and Novelty in the Evolution of Cell Adhesion and Extracellular Matrix Genes
Hutter, H., Vogel, B. E., Plenefisch, J. D., Norris, C. R., Proenca, R. B., Spieth, J., Guo, C. B., Mastwal, S. S., Zhu, X., Scheel, J., et al. (2000) · Science · doi:10.1126/science.287.5455.989 · Cited by 262
Navratil, J. S., Watkins, S. C., Wisnieski, J. J., & Ahearn, J. M. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.5.3231 · Cited by 262
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Tasic, B., Hippenmeyer, S., Wang, C., Gamboa, M., Zong, H., Chen-Tsai, Y., & Luo, L. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1019507108 · Cited by 246
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BackgroundVerbovetski, I., Bychkov, H., Trahtemberg, U., Shapira, I., Hareuveni, M., Ben‐Tal, O., Kutikov, I., Gill, O., & Mevorach, D. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20020263 · Cited by 261
DNA triplet repeats mediate heterochromatin-protein-1-sensitive variegated gene silencing
Saveliev, A., Everett, C. M., Sharpe, T., Webster, Z., & Festenstein, R. (2003) · Nature · doi:10.1038/nature01596 · Cited by 258
“Certain transgenes are prone to variegation when repeated in tandem array”
BackgroundDillon, N., & Festenstein, R. (2002) · Trends in Genetics · doi:10.1016/s0168-9525(02)02648-3 · Cited by 260
Houdebine, L. (2000) · Transgenic Research · doi:10.1023/a:1008934912555 · Cited by 255
“A transgene seems to have less chance to be expressed efficiently if it contains non animal sequences, if it is devoid of intron and if it is integrated in multicopy (Dorer, 1997; Garrick et al., 1998).”
BackgroundSzondy, Z., Sarang, Z., Molnár, P., Németh, T., Piacentini, M., Mastroberardino, P. G., Falasca, L., Aeschlimann, D. P., Kovács, J., Kiss, I., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0832466100 · Cited by 251
Inducible and Reversible Gene Expression with the rtTA System for the Study of Memory
Mansuy, I. M., Winder, D. G., Moallem, T. M., Osman, M., Mayford, M. R., Hawkins, R. D., & Kandel, E. R. (1998) · Neuron · doi:10.1016/s0896-6273(00)80533-4 · Cited by 252
Deficiency in Serum Immunoglobulin (Ig)m Predisposes to Development of Igg Autoantibodies
Ehrenstein, M. R., Cook, H. T., & Neuberger, M. S. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.191.7.1253 · Cited by 246
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Benoit, M. E., Clarke, E. V., Morgado, P., Fraser, D. A., & Tenner, A. J. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1103760 · Cited by 253
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Day, C. D., Lee, E., Kobayashi, J., Holappa, L. D., Albert, H. H., & Ow, D. W. (2000) · Genes & Development · doi:10.1101/gad.849600 · Cited by 242
“In Drosophila, plants, and mice, experiments with variable transgene repeats at the same locus support this hypothesis (Assaad et al. 1993; Sabl and Henikoff 1996; Garrick et al. 1998).”
BackgroundResultWalsh, M. C., Bourcier, T., Takahashi, K., Shi, L., Busche, M. N., Rother, R. P., Solomon, S. D., Ezekowitz, R. A. B., & Stahl, G. L. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.1.541 · Cited by 239
Apoptotic cells induce Mer tyrosine kinase–dependent blockade of NF-κB activation in dendritic cells
Sen, P., Wallet, M. A., Yi, Z., Huang, Y., Henderson, M., Mathews, C. E., Earp, H. S., Matsushima, G. K., Baldwin, A. S., & Tisch, R. (2006) · Blood · doi:10.1182/blood-2006-04-017368 · Cited by 240
Opsonization with C1q and Mannose-Binding Lectin Targets Apoptotic Cells to Dendritic Cells
Nauta, A. J., Castellano, G., Xu, W., Woltman, A. M., Borrias, M. C., Daha, M. R., van Kooten, C., & Roos, A. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.5.3044 · Cited by 236
Targeting genes for self-excision in the germ linePreprint
Bunting, M., Bernstein, K. E., Greer, J. M., Capecchi, M. R., & Thomas, K. R. (1999) · Genes & Development · doi:10.1101/gad.13.12.1524 · Cited by 234
“…of chromosomal rearrangements typically mediated by Cre-catalyzed recombination (Ramrez-Solis et al. 1995; Smith et al. 1995; Hé rault et al. 1998) or in the condensation of tandem repeats resulting from the random integration of transgenes following pronuclear injection (Garrick et al. 1998).”
BackgroundSleeping Beauty Transposition: Biology and Applications for Molecular Therapy
Izsvák, Z., & Ivics, Z. (2004) · Molecular Therapy · doi:10.1016/j.ymthe.2003.11.009 · Cited by 241
Transposon-mediated BAC transgenesis in zebrafish
Suster, M. L., Abe, G., Schouw, A., & Kawakami, K. (2011) · Nature Protocols · doi:10.1038/nprot.2011.416 · Cited by 226
“Concatemeric transgenes are generally associated with silencing, instability and genetic lesions both inside and around the transgene”
BackgroundComplement Component C3 Mediates Inflammatory Injury Following Focal Cerebral Ischemia
Mocco, J., Mack, W. J., Ducruet, A. F., Sosunov, S. A., Sughrue, M. E., Hassid, B. G., Nair, M. N., Laufer, I., Komotar, R. J., Claire, M. B. F. S., et al. (2006) · Circulation Research · doi:10.1161/01.res.0000232544.90675.42 · Cited by 226
Control of signaling-mediated clearance of apoptotic cells by the tumor suppressor p53
Yoon, K. W., Byun, S., Kwon, E., Hwang, S.-Y., Chu, K., Hiraki, M., Jo, S., Weins, A., Hakroush, S., Cebulla, A., et al. (2015) · Science · doi:10.1126/science.1261669 · Cited by 230
C1q Deficiency and Autoimmunity: The Effects of Genetic Background on Disease Expression
Mitchell, D. A., Pickering, M. C., Warren, J. A., Fossati‐Jimack, L., Cortés-Hernández, J., Cook, H. T., Botto, M., & Walport, M. J. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.5.2538 · Cited by 223
Taming of transposable elements by homology-dependent gene silencing
Jensen, S., Gassama, M.-P., & Heidmann, T. (1999) · Nature Genetics · doi:10.1038/5997 · Cited by 222
“In some cases, homology-dependent gene silencing did not require transcription of the transgene, but occurred under specific conditions where 'silencing' sequences were introduced as tandem repeats or concatamer”
BackgroundChen, Y., Park, Y., Patel, E. S., & Silverman, G. J. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0804191 · Cited by 221
Epigenetics: molecular mechanisms and implications for disease
Handel, A. E., Ebers, G. C., & Ramagopalan, S. V. (2009) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2009.11.003 · Cited by 227
Zhang, J., Thomas, T. Z., Kasper, S., & Matusik, R. J. (2000) · Endocrinology · doi:10.1210/endo.141.12.7837 · Cited by 219
“Furthermore, numerous transgenes in tandem may condense into euchromatin, thereby silencing transcription through interactions between the repeats (24, 25).”
Nucleosomes Are Exposed at the Cell Surface in Apoptosis
Radic, M. Z., Marion, T. N., & Monestier, M. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.11.6692 · Cited by 218
Kim, M., O’Callaghan, P. M., Droms, K. A., & James, D. C. (2011) · Biotechnology and Bioengineering · doi:10.1002/bit.23189 · Cited by 215
“reductions in overall transgene expression in comparison to cell lines where the number of repeats is much lower, although even at low copy number the per gene expression level can still be significantly reduced relative to the single copy number expression level through silencing (Garrick et al., 1998; McBurney et al…”
BackgroundMorimoto, K., Janssen, W. J., Fessler, M. B., McPhillips, K. A., Borges, V. M., Bowler, R. P., Xiao, Y., Kench, J. A., Henson, P. M., & Vandivier, R. W. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.12.7657 · Cited by 215
Cd5 Maintains Tolerance in Anergic B Cells
Hippen, K. L., Tze, L. E., & Behrens, T. W. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.191.5.883 · Cited by 214
Transgenic expression of JAK2V617F causes myeloproliferative disorders in mice.
Xing, S., Wanting, T. H., Zhao, W.-M., Ma, J., Wang, S.-F., Xu, X., Li, Q.-S., Fu, X.-Q., Xu, M.-J., & Zhao, Z. (2007) · Blood · doi:10.1182/blood-2007-05-091579 · Cited by 223
“Position-effect variegation caused by repeat-induced gene silencing (24) and normal variations among mice due to epigenetic factors may contribute to such a phenomenon.”
BackgroundThe evolution of human anti-double-stranded DNA autoantibodies
Wellmann, U., Letz, M., i, M. H., Angermüller, S., Kalden, J. R., & Winkler, T. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500132102 · Cited by 210
Watanabe, H., Garnier, G., Circolo, A., Wetsel, R. A., Ruiz, P., Holers, V. M., Boackle, S. A., Colten, H. R., & Gilkeson, G. S. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.2.786 · Cited by 208
Stuart, L. M., Takahashi, K., Shi, L., Savill, J., & Ezekowitz, R. A. B. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.6.3220 · Cited by 205
Regulation of heterochromatin by histone methylation and small RNAs
Grewal, S. I. S., & Rice, J. C. (2004) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2004.04.002 · Cited by 207
Chromatin loops are selectively anchored using scaffold/matrix-attachment regions
Heng, H. H., Götze, S., Ye, C. J., Liu, G., Stevens, J. B., Bremer, S. W., Wykes, S. M., Bode, J., & Krawetz, S. A. (2004) · Journal of Cell Science · doi:10.1242/jcs.00976 · Cited by 204
“Short tandem repeated arrays of transgene have been reported to form heterochromatin and silence gene expression (Henikoff, 1998; Garrick et al., 1998).”
BackgroundWood, W., Turmaine, M., Weber, R., Camp, V., Maki, R. A., McKercher, S. R., & Martin, P. B. (2000) · Development · doi:10.1242/dev.127.24.5245 · Cited by 201
C1q restrains autoimmunity and viral infection by regulating CD8 + T cell metabolism
Ling, G. S., Crawford, G., Buang, N., Bartok, I., Tian, K., Thielens, N. M., Bally, I., Harker, J. A., Ashton-Rickardt, P. G., Rutschmann, S., et al. (2018) · Science · doi:10.1126/science.aao4555 · Cited by 199
Hart, M. L., Ceonzo, K., Shaffer, L. A., Takahashi, K., Rother, R. P., Reenstra, W. R., Buras, J. A., & Stahl, G. L. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.10.6373 · Cited by 195
Mobile elements and the human genome
Prak, E. T. L., & Kazazian, H. H. (2000) · Nature Reviews Genetics · doi:10.1038/35038572 · Cited by 203
“Transposon and retrotransposon insertions are typically single copy, unlike most DNA-based transfection methods, and therefore potentially less liable to be inactivated by methylatio”
BackgroundAn N -ethyl- N -nitrosourea screen for genes involved in variegation in the mouse
Blewitt, M. E., Vickaryous, N. K., Hemley, S. J., Ashe, A., Bruxner, T. J., Preis, J. I., Arkell, R., & Whitelaw, E. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409375102 · Cited by 186
Self-citation
Metadata
- Authors
- Garrick, D., Fiering, S., Martin, D. I. K., & Whitelaw, E.
- Affiliations
- The University of Sydney (AU)
- Dartmouth–Hitchcock Medical Center (US)
- Fred Hutch Cancer Center (US)
- Venue
- Nature Genetics
- Published
- 1998-01
- Volume
- 18
- Issue
- 1
- Pages
- 56-59
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2065189089
- Cited by
- 887
- References
- 32
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 20 · 2023: 16 · 2022: 9 · 2021: 16 · 2020: 16 · 2019: 14 · 2018: 20 · 2017: 23 · 2016: 25 · 2015: 28 · 2014: 24 · 2013: 24 · 2012: 41
- FWCI
- 36.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
- Keywords
- transgene copy number, transgene silencing, position effect, transgenic mice, chromatin condensation, DNA methylation, epigenetic silencing
- MeSH terms
- Animals, Chromatin, Erythrocytes, Female, Gene Expression Regulation, Humans, Lac Operon, Male, Mammals, Mice, Transgenic, Repetitive Sequences, Nucleic Acid, Transcription, Genetic, Viral Proteins, Gene Dosage, Transgenes, Integrases, Mice
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