Transcriptional disruption by the L1 retrotransposon and implications for mammalian transcriptomes
Abstract
LINE-1 (L1) elements are the most abundant autonomous retrotransposons in the human genome, accounting for about 17% of human DNA. The L1 retrotransposon encodes two proteins, open reading frame (ORF)1 and the ORF2 endonuclease/reverse transcriptase. L1 RNA and ORF2 protein are difficult to detect in mammalian cells, even in the context of overexpression systems. Here we show that inserting L1 sequences on a transcript significantly decreases RNA expression and therefore protein expression. This decreased RNA concentration does not result from major effects on the transcription initiation rate or RNA stability. Rather, the poor L1 expression is primarily due to inadequate transcriptional elongation. Because L1 is an abundant and broadly distributed mobile element, the inhibition of transcriptional elongation by L1 might profoundly affect expression of endogenous human genes. We propose a model in which L1 affects gene expression genome-wide by acting as a 'molecular rheostat' of target genes. Bioinformatic data are consistent with the hypothesis that L1 can serve as an evolutionary fine-tuner of the human transcriptome.
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L1 retrotransposon activity has been linked to DNA damage, mutagenesis, and deregulation of host gene transcription.
“Long interspersed element 1 (L1) retrotransposon activity, in particular, has been linked to DNA damage5, mutagenesis6,7, and deregulation of host gene transcription8.”
From SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age (2014) · cites this paper as [8]
Cites
Initial sequencing and analysis of the human genome
International Human Genome Sequencing Consortium, Whitehead Institute for Biomedical Research, C. F. G. R., Lander, E. S., Linton, L. M., Birren, B., Nusbaum, C., Zody, M. C., Baldwin, J., Devon, K., Dewar, K., et al. (2001) · Nature · doi:10.1038/35057062 · Cited by 24,216 · see citing works
Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs
Okazaki, Y., Furuno, M., Kasukawa, T., Adachi, J., Bono, H. U., Kondo, S., Nikaido, I., Osato, N., Saito, R., Suzuki, H., et al. (2002) · Nature · doi:10.1038/nature01266 · Cited by 1,636 · see citing works
Luan, D. D., Korman, M. H., Jakubczak, J. L., & Eickbush, T. H. (1993) · Cell · doi:10.1016/0092-8674(93)90078-5 · Cited by 1,173 · see citing works
Human L1 retrotransposon encodes a conserved endonuclease required for retrotransposition
Feng, Q., Moran, J. V., Kazazian, H. H., & Boeke, J. D. (1996) · Cell · doi:10.1016/s0092-8674(00)81997-2 · Cited by 1,139 · see citing works
Self-citationLINE-mediated retrotransposition of marked Alu sequences
Dewannieux, M., Esnault, C., & Heidmann, T. (2003) · Nature Genetics · doi:10.1038/ng1223 · Cited by 1,026 · see citing works
High frequency retrotransposition in cultured mammalian cells
Moran, J. V., Holmes, S. E., Naas, T. P., DeBerardinis, R. J., Boeke, J. D., & Kazazian, H. H. (1996) · Cell · doi:10.1016/s0092-8674(00)81998-4 · Cited by 1,022 · see citing works
Self-citationHuman LINE retrotransposons generate processed pseudogenes
Esnault, C., Maestre, J., & Heidmann, T. (2000) · Nature Genetics · doi:10.1038/74184 · Cited by 835 · see citing works
Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system
Agrawal, A., Eastman, Q. M., & Schatz, D. G. (1998) · Nature · doi:10.1038/29457 · Cited by 811 · see citing works
Reverse Transcriptase Encoded by a Human Transposable Element
Mathias, S. L., Scott, A. F., Kazazian, H. H., Boeke, J. D., & Gabriel, A. (1991) · Science · doi:10.1126/science.1722352 · Cited by 774 · see citing works
Self-citationHuman L1 Retrotransposition: cis Preference versus trans Complementation
Wei, W., Gilbert, N., Ooi, S. L., Lawler, J. F., Ostertag, E. M., Kazazian, H. H., Boeke, J. D., & Moran, J. V. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.4.1429-1439.2001 · Cited by 637 · see citing works
Self-citationExon Shuffling by L1 Retrotransposition
Moran, J. V., DeBerardinis, R. J., & Kazazian, H. H. (1999) · Science · doi:10.1126/science.283.5407.1530 · Cited by 629 · see citing works
Allelic Variation in Human Gene Expression
Yan, H., Yuan, W., Velculescu, V. E., Vogelstein, B., & Kinzler, K. W. (2002) · Science · doi:10.1126/science.1072545 · Cited by 625 · see citing works
Sassanfar, M., & Szostak, J. W. (1993) · Nature · doi:10.1038/364550a0 · Cited by 593 · see citing works
Human L1 element target‐primed reverse transcription in vitro
Cost, G. J., Feng, Q., Jacquier, A., & Boeke, J. D. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf592 · Cited by 519 · see citing works
Self-citationSELFISH DNA: A SEXUALLY-TRANSMITTED NUCLEAR PARASITE
Hickey, D. A. (1982) · Genetics · doi:10.1093/genetics/101.3-4.519 · Cited by 497 · see citing works
Human L1 Retrotransposition Is Associated with Genetic Instability In Vivo
Symer, D. E., Connelly, C. J., Szak, S. T., Caputo, E. M., Cost, G. J., Parmigiani, G., & Boeke, J. D. (2002) · Cell · doi:10.1016/s0092-8674(02)00839-5 · Cited by 479 · see citing works
Self-citationGenomic Deletions Created upon LINE-1 Retrotransposition
Gilbert, N., Lutz-Prigge, S., & Moran, J. V. (2002) · Cell · doi:10.1016/s0092-8674(02)00828-0 · Cited by 474 · see citing works
Transposons in place of telomeric repeats at a Drosophila telomere
Levis, R. W., Ganesan, R., Houtchens, K. A., Tolar, L. A., & Sheen, F.-M. (1993) · Cell · doi:10.1016/0092-8674(93)90318-k · Cited by 448 · see citing works
Allelic Variation in Gene Expression Is Common in the Human GenomePreprint
Lo, H. S., Wang, Z., Hu, Y., Yang, H. H., Gere, S., Buetow, K. H., & Lee, M. P. (2003) · Genome Research · doi:10.1101/gr.1006603 · Cited by 446 · see citing works
Identification, Characterization, and Cell Specificity of a Human LINE-1 Promoter
Swergold, G. D. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.12.6718 · Cited by 439 · see citing works
Positional cloning of the gene for X-linked retinitis pigmentosa 2
Schwahn, U., Lenzner, S., Dong, J., Feil, S., Hinzmann, B., van Duijnhoven, G., Kirschner‐Schwabe, R., Hemberger, M., Bergen, A. A. B., Rosenberg, T., et al. (1998) · Nature Genetics · doi:10.1038/1214 · Cited by 384 · see citing works
Nucleic Acid Chaperone Activity of the ORF1 Protein from the Mouse LINE-1 Retrotransposon
Martin, S. L., & Bushman, F. D. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.2.467-475.2001 · Cited by 348 · see citing works
L1 (LINE-1) Retrotransposon Evolution and Amplification in Recent Human History
Boissinot, S., Chevret, P., & Furano, A. V. (2000) · Molecular Biology and Evolution · doi:10.1093/oxfordjournals.molbev.a026372 · Cited by 312 · see citing works
Frequent Human Genomic DNA Transduction Driven by LINE-1 RetrotranspositionPreprint
Pickeral, O. K., Makałowski, W., Boguski, M. S., & Boeke, J. D. (2000) · Genome Research · doi:10.1101/gr.10.4.411 · Cited by 279 · see citing works
Self-citationTransduction of 3'-flanking sequences is common in L1 retrotransposition
Goodier, J. L. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.4.653 · Cited by 266 · see citing works
Lo, J., Lee, S.-C., Xu, M., Liu, F., Ruan, H., Eun, A., He, Y., Ma, W., Wang, W., Wen, Z., et al. (2003) · Genome Research · doi:10.1101/gr.885403 · Cited by 265 · see citing works
RNA truncation by premature polyadenylation attenuates human mobile element activity
Belancio, V. P., & Deininger, P. L. (2003) · Nature Genetics · doi:10.1038/ng1269 · Cited by 263 · see citing works
Cost, G. J., & Boeke, J. D. (1998) · Biochemistry · doi:10.1021/bi981858s · Cited by 242 · see citing works
Self-citationBranciforte, D., & Martin, S. L. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.4.2584 · Cited by 231 · see citing works
Molecular archeology of L1 insertions in the human genome
Szak, S. T., Pickeral, O. K., Makalowski, W., Boguski, M. S., Landsman, D., & Boeke, J. D. (2002) · Genome Biology · doi:10.1186/gb-2002-3-10-research0052 · Cited by 230 · cited 1× · see citing works
“This explains, at least in part, the distribution of predominantly non-functional, 5′ truncated L1s in the genom”
BackgroundSelf-citationA highly active synthetic mammalian retrotransposon
Han, J. S., & Boeke, J. D. (2004) · Nature · doi:10.1038/nature02535 · Cited by 181 · see citing works
Self-citationSelection Against Deleterious LINE-1-Containing Loci in the Human Lineage
Boissinot, S., Entezam, A., & Furano, A. V. (2001) · Molecular Biology and Evolution · doi:10.1093/oxfordjournals.molbev.a003893 · Cited by 179 · see citing works
Kolosha, V. O., & Martin, S. L. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.19.10155 · Cited by 167 · see citing works
An important role for RUNX3 in human L1 transcription and retrotransposition
Yang, N. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg663 · Cited by 167 · see citing works
Members of the SRY family regulate the human LINE retrotransposons
Tchénio, T. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.2.411 · Cited by 162 · see citing works
Zarudnaya, M. I. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg241 · Cited by 162 · see citing works
Trelogan, S., & Martin, S. L. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.5.1520 · Cited by 144 · see citing works
Burwinkel, B., & Kilimann, M. W. (1998) · Journal of Molecular Biology · doi:10.1006/jmbi.1998.1641 · Cited by 138 · see citing works
Kolosha, V. O., & Martin, S. L. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210487200 · Cited by 124 · see citing works
Chávez, S., García-Rubio, M. L., Prado, F., & Aguilera, A. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.20.7054-7064.2001 · Cited by 114 · see citing works
Yajima, I., Sato, S., Kimura, T., Yasumoto, K., Shibahara, S., Goding, C. R., & Yamamoto, H. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.8.1431 · Cited by 113 · see citing works
Minakami, R., Kurose, K., Etoh, K., Furuhata, Y., Hattori, M., & Sakaki, Y. (1992) · Nucleic Acids Research · doi:10.1093/nar/20.12.3139 · Cited by 112 · see citing works
Secreted and membrane attractin result from alternative splicing of the human ATRN gene
Tang, W., Gunn, T. M., McLaughlin, D. F., Barsh, G. S., Schlossman, S. F., & Duke‐Cohan, J. S. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.110139897 · Cited by 80 · see citing works
Miller, T., Williams, K., Johnstone, R. W., & Shilatifard, A. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m005175200 · Cited by 76 · see citing works
Sex brings transposons and genomes into conflict
Bestor, T. H. (2000) · Springer eBooks · doi:10.1007/978-94-011-4156-7_28 · Cited by 65 · see citing works
Sex brings transposons and genomes into conflict
Bestor, T. H. (1999) · Genetica · doi:10.1023/a:1003990818251 · Cited by 62 · see citing works
Isochore chromosome maps of the human genome
Oliver, J. L. T., Carpena, P., Ramón Román-roldán, C., Mata‐Balaguer, T., Mejı́as-Romero, A., Hackenberg, M., & Bernaola‐Galván, P. (2002) · Gene · doi:10.1016/s0378-1119(02)01034-x · Cited by 62 · see citing works
Clements, A. (1998) · Nucleic Acids Research · doi:10.1093/nar/26.15.3528 · Cited by 59 · see citing works
Transcription of the human U2 snRNA genes continues beyond the 3′ box in vivo
Cuello, P., Boyd, D. C., Dye, M. J., Proudfoot, N. J., & Murphy, S. (1999) · The EMBO Journal · doi:10.1093/emboj/18.10.2867 · Cited by 59 · see citing works
Mutant ATP-binding RNA aptamers reveal the structural basis for ligand binding
Dieckmann, T., Butcher, S. E., Sassanfar, M., Szostak, J. W., & Feigon, J. F. (1997) · Journal of Molecular Biology · doi:10.1006/jmbi.1997.1329 · Cited by 52 · see citing works
Cloning and identification of testis-specific transcription elongation factor S-II.
Xu, Q., Nakanishi, T., Sekimizu, K., & Natori, S. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)42053-9 · Cited by 40 · see citing works
Flagged first, then by citations
1 of the 52 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
The impact of retrotransposons on human genome evolution
Cordaux, R., & Batzer, M. (2009) · Nature reviews genetics · doi:10.1038/nrg2640 · Cited by 1,691 · see citing works
Synonymous but not the same: the causes and consequences of codon bias
Plotkin, J. B., & Kudla, G. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2899 · Cited by 1,677 · see citing works
Regulatory activities of transposable elements: from conflicts to benefits
Chuong, E. B., Elde, N. C., & Feschotte, C. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.139 · Cited by 1,343 · see citing works
Somatic mosaicism in neuronal precursor cells mediated by L1 retrotransposition
Muotri, A. R., Chu, V. T., Marchetto, M. C. N., Deng, W., Moran, J. V., & Gage, F. H. (2005) · Nature · doi:10.1038/nature03663 · Cited by 942 · see citing works
Long-Range Control of Gene Expression: Emerging Mechanisms and Disruption in Disease
Kleinjan, D. A., & van Heyningen, V. (2004) · The American Journal of Human Genetics · doi:10.1086/426833 · Cited by 868 · see citing works
The regulated retrotransposon transcriptome of mammalian cells
Faulkner, G. J., Kimura, Y., Daub, C. O., Wani, S., Plessy, C., Irvine, K. M., Schroder, K., Cloonan, N., Steptoe, A. L., Lassmann, T., et al. (2009) · Nature Genetics · doi:10.1038/ng.368 · Cited by 819 · see citing works
Landscape of Somatic Retrotransposition in Human Cancers
Lee, E., Iskow, R., Yang, L., Gokcumen, O., Haseley, P., Luquette, L. J., Lohr, J. G., Harris, C. C., Ding, L., Wilson, R. K., et al. (2012) · Science · doi:10.1126/science.1222077 · Cited by 762 · see citing works
Somatic retrotransposition alters the genetic landscape of the human brain
Baillie, J. K., Barnett, M. W., Upton, K. R., Gerhardt, D. J., Richmond, T. A., De Sapio, F., Brennan, P. M., Rizzu, P., Smith, S., Fell, M., et al. (2011) · Nature · doi:10.1038/nature10531 · Cited by 684 · see citing works
The profile of repeat‐associated histone lysine methylation states in the mouse epigenome
Martens, J. H. A., O’Sullivan, R. J., Braunschweig, U., Opravil, S., Radolf, M., Steinlein, P., & Jenuwein, T. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600545 · Cited by 663 · see citing works
Rapid DNA methylation changes after exposure to traffic particles
Baccarelli, A., Wright, R. O., Bollati, V., Tarantini, L., Litonjua, A. A., Suh, H. H., Zanobetti, A., Sparrow, D., Vokonas, P. S., & Schwartz, J. (2009) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200807-1097oc · Cited by 653 · see citing works
L1 retrotransposition in neurons is modulated by MeCP2
Muotri, A. R., Marchetto, M. C. N., Coufal, N. G., Oefner, R., Yeo, G., Nakashima, K., & Gage, F. H. (2010) · Nature · doi:10.1038/nature09544 · Cited by 626 · see citing works
Retrotransposons Revisited: The Restraint and Rehabilitation of Parasites
Goodier, J. L., & Kazazian, H. H. (2008) · Cell · doi:10.1016/j.cell.2008.09.022 · Cited by 627 · see citing works
Dynamic interactions between transposable elements and their hosts
Levin, H. L., & Moran, J. V. (2011) · Nature Reviews Genetics · doi:10.1038/nrg3030 · Cited by 621 · see citing works
LINE-1 elements in structural variation and disease
Beck, C. R., Garcia-Perez, J. L., Badge, R. M., & Moran, J. V. (2011) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-082509-141802 · Cited by 615 · see citing works
Schmidt, D., Schwalie, P. C., Wilson, M. D., Ballester, B., Gonçalves, Â., Kutter, C., Brown, G. D., Marshall, A., Flicek, P., & Odom, D. T. (2012) · Cell · doi:10.1016/j.cell.2011.11.058 · Cited by 598 · see citing works
Comparative Genomics and Molecular Dynamics of DNA Repeats in Eukaryotes
Richard, G., Kerrest, A., & Dujon, B. (2008) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00011-08 · Cited by 549 · see citing works
Widespread RNA Editing of EmbeddedAluElements in the Human TranscriptomePreprint
Kim, D. D. Y., Kim, T. T. Y., Walsh, T., Kobayashi, Y., Matise, T. C., Buyske, S. G., & Gabriel, A. (2004) · Genome Research · doi:10.1101/gr.2855504 · Cited by 534 · see citing works
Ogino, S., Chan, A. T., Fuchs, C. S., & Giovannucci, E. L. (2010) · Gut · doi:10.1136/gut.2010.217182 · Cited by 521 · see citing works
High Guanine and Cytosine Content Increases mRNA Levels in Mammalian Cells
Kudla, G., Lipinski, L., Caffin, F., Helwak, A., & Zylicz, M. (2006) · PLoS Biology · doi:10.1371/journal.pbio.0040180 · Cited by 476 · see citing works
Intragenic DNA methylation alters chromatin structure and elongation efficiency in mammalian cells
Lorincz, M. C., Dickerson, D. R., Schmitt, M., & Groudine, M. T. (2004) · Nature Structural & Molecular Biology · doi:10.1038/nsmb840 · Cited by 460 · see citing works
Van Meter, M., Kashyap, M., Rezazadeh, S., Geneva, A. J., Morello, T. D., Seluanov, A., & Gorbunova, V. (2014) · Nature Communications · doi:10.1038/ncomms6011 · Cited by 455 · see citing works
“Long interspersed element 1 (L1) retrotransposon activity, in particular, has been linked to DNA damage 5 , mutagenesis 6,7 , and deregulation of host gene transcription 8 .”
Mobile DNA in Health and Disease
Kazazian, H. H., & Moran, J. V. (2017) · New England Journal of Medicine · doi:10.1056/nejmra1510092 · Cited by 445 · see citing works
Restricting retrotransposons: a review
Goodier, J. L. (2016) · Mobile DNA · doi:10.1186/s13100-016-0070-z · Cited by 436 · see citing works
NONCODING RNAS IN THE MAMMALIAN CENTRAL NERVOUS SYSTEM
Cao, X., Yeo, G. W.-M., Muotri, A. R., Kuwabara, T., & Gage, F. H. (2006) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.29.051605.112839 · Cited by 432 · see citing works
Yang, N., & Kazazian, H. H. (2006) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1141 · Cited by 398 · see citing works
Endogenous Retrotransposition Activates Oncogenic Pathways in Hepatocellular Carcinoma
Shukla, R., Upton, K. R., Muñoz-López, M., Gerhardt, D. J., Fisher, M. E., Nguyen, T., Brennan, P. M., Baillie, J. K., Collino, A., Ghisletti, S., et al. (2013) · Cell · doi:10.1016/j.cell.2013.02.032 · Cited by 391 · see citing works
Why repetitive DNA is essential to genome function
Shapiro, J. A., & von Sternberg, R. (2005) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1017/s1464793104006657 · Cited by 366 · see citing works
Bulut-Karslioglu, A., De La Rosa-Velázquez, I. A., Ramirez, F., Barenboim, M., Onishi-Seebacher, M., Arand, J., Galán, C., Winter, G. E., Engist, B., Gerle, B., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.05.029 · Cited by 368 · see citing works
Ischemic Heart Disease and Stroke in Relation to Blood DNA Methylation
Baccarelli, A., Wright, R. O., Bollati, V., Litonjua, A. A., Zanobetti, A., Tarantini, L., Sparrow, D., Vokonas, P., & Schwartz, J. D. (2010) · Epidemiology · doi:10.1097/ede.0b013e3181f20457 · Cited by 361 · see citing works
Gibbon genome and the fast karyotype evolution of small apes
Carbone, L., Harris, R. A., Gnerre, S., Veeramah, K. R., Lorente-Galdós, B., Huddleston, J., Meyer, T. J., Herrero, J., Roos, C., Aken, B. L., et al. (2014) · Nature · doi:10.1038/nature13679 · Cited by 360 · see citing works
Selective silencing of euchromatic L1s revealed by genome-wide screens for L1 regulators
Liu, N., Lee, C. H., Swigut, T., Grow, E. J., Gu, B., Bassik, M. C., & Wysocka, J. (2017) · Nature · doi:10.1038/nature25179 · Cited by 355 · see citing works
APOBEC3 Proteins Inhibit Human LINE-1 Retrotransposition
Muckenfuß, H., Hamdorf, M., Held, U., Perković, M., Löwer, J., Cichutek, K., Flory, E., Schumann, G. G., & Münk, C. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m601716200 · Cited by 353 · see citing works
Mammalian non-LTR retrotransposons: For better or worse, in sickness and in healthPreprint
Belancio, V. P., Hedges, D. J., & Deininger, P. L. (2008) · Genome Research · doi:10.1101/gr.5558208 · Cited by 317 · see citing works
Ubiquitous L1 Mosaicism in Hippocampal Neurons
Upton, K. R., Gerhardt, D. J., Jesuadian, J. S., Richardson, S. R., Sánchez-Luque, F. J., Bodea, G. O., Ewing, A. D., Salvador-Palomeque, C., van der Knaap, M. S., Brennan, P. M., et al. (2015) · Cell · doi:10.1016/j.cell.2015.03.026 · Cited by 320 · see citing works
The Influence of LINE-1 and SINE Retrotransposons on Mammalian Genomes
Richardson, S. R., Doucet, A. J., Kopera, H. C., Moldovan, J. B., Garcia-Perez, J. L., & Moran, J. V. (2015) · Microbiology Spectrum · doi:10.1128/microbiolspec.mdna3-0061-2014 · Cited by 313 · see citing works
Mobile elements create structural variation: Analysis of a complete human genomePreprint
Xing, J., Zhang, Y., Han, K., Salem, A. H., Sen, S. K., Huff, C., Zhou, Q., Kirkness, E. F., Levy, S., Batzer, M. A., et al. (2009) · Genome Research · doi:10.1101/gr.091827.109 · Cited by 313 · see citing works
Ewing, A. D., & Kazazian, H. H. (2010) · Genome Research · doi:10.1101/gr.106419.110 · Cited by 301 · see citing works
Burns, K. H., & Boeke, J. D. (2012) · Cell · doi:10.1016/j.cell.2012.04.019 · Cited by 295 · see citing works
Self-citationRetroviral insertional mutagenesis: past, present and future
Uren, A. G., Kool, J., Berns, A. J. M., & van Lohuizen, M. (2005) · Oncogene · doi:10.1038/sj.onc.1209043 · Cited by 271 · see citing works
LINE-1 retrotransposons: mediators of somatic variation in neuronal genomes?
Singer, T., McConnell, M. J., Marchetto, M. C., Coufal, N. G., & Gage, F. H. (2010) · Trends in Neurosciences · doi:10.1016/j.tins.2010.04.001 · Cited by 268 · see citing works
Causes and consequences of DNA hypomethylation in human cancer
Hoffmann, M. J., & Schulz, W. A. (2005) · Biochemistry and Cell Biology · doi:10.1139/o05-036 · Cited by 252 · see citing works
Mobile Interspersed Repeats Are Major Structural Variants in the Human Genome
Huang, C. R. L., Schneider, A. M., Lu, Y., Niranjan, T., Shen, P., Robinson, M. A., Steranka, J. P., Valle, D. L., Civin, C. I., Wang, T., et al. (2010) · Cell · doi:10.1016/j.cell.2010.05.026 · Cited by 250 · see citing works
Self-citationTransposable elements as a potent source of diverse cis -regulatory sequences in mammalian genomes
Sundaram, V., & Wysocka, J. (2020) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2019.0347 · Cited by 238 · see citing works
Sela, N., Mersch, B., Gal-Mark, N., Lev-Maor, G., Hotz‐Wagenblatt, A., & Ast, G. (2007) · Genome biology · doi:10.1186/gb-2007-8-6-r127 · Cited by 233 · see citing works
Retrotransposable Elements and Human Disease
Callinan, P. A., & Batzer, M. A. (2006) · KARGER eBooks · doi:10.1159/000092503 · Cited by 232 · see citing works
Chen, J., Stenson, P. D., Cooper, D. N., & Férec, C. (2005) · Human Genetics · doi:10.1007/s00439-005-1321-0 · Cited by 226 · see citing works
The ecology of the genome — mobile DNA elements and their hosts
Brookfield, J. F. Y. (2005) · Nature Reviews Genetics · doi:10.1038/nrg1524 · Cited by 224 · see citing works
Methylation of Endogenous Human Retroelements in Health and Disease
Schulz, W. A., Steinhoff, C., & Florl, A. R. (2006) · Springer eBooks · doi:10.1007/3-540-31181-5_11 · Cited by 222 · see citing works
Principles of RNA processing from analysis of enhanced CLIP maps for 150 RNA binding proteins
Nostrand, E. L. V., Pratt, G. A., Yee, B. A., Wheeler, E. C., Blue, S. M., Mueller, J. R., Park, S. S., Garcia, K. E., Gelboin-Burkhart, C. A., Nguyen, T. B., et al. (2020) · Genome biology · doi:10.1186/s13059-020-01982-9 · Cited by 213 · see citing works
Ogino, S., Lochhead, P. J., Chan, A. T., Nishihara, R., Cho, E., Wolpin, B. M., Meyerhardt, J. A., Meissner, A., Schernhammer, E. S., Fuchs, C. S., et al. (2013) · Modern Pathology · doi:10.1038/modpathol.2012.214 · Cited by 213 · see citing works
LINE-1 RNA splicing and influences on mammalian gene expression
Belancio, V. P. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl027 · Cited by 209 · see citing works
How retrotransposons shape genome regulation
Mita, P., & Boeke, J. D. (2016) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2016.01.001 · Cited by 205 · see citing works
Self-citationProgress in understanding the biology of the human mutagen LINE-1
Babushok, D. V., & Kazazian, H. H. (2007) · Human Mutation · doi:10.1002/humu.20486 · Cited by 207 · see citing works
LINE-1 retrotransposons: Modulators of quantity and quality of mammalian gene expression?
Han, J. S., & Boeke, J. D. (2005) · BioEssays · doi:10.1002/bies.20257 · Cited by 206 · see citing works
Self-citationThe impact of transposable elements on mammalian development
Garcia-Perez, J. L., Widmann, T. J., & Adams, I. R. (2016) · Development · doi:10.1242/dev.132639 · Cited by 196 · see citing works
Global Methylation Patterns in Idiopathic Pulmonary Fibrosis
Rabinovich, E. I., Kapetanaki, M. G., Steinfeld, I., Gibson, K. F., Pandit, K. V., Yu, G., Zohar Yakhini, B., & Kaminski, N. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033770 · Cited by 197 · see citing works
Revisiting the evolution of mouse LINE-1 in the genomic era
Sookdeo, A., Hepp, C. M., McClure, M. A., & Boissinot, S. (2013) · Mobile DNA · doi:10.1186/1759-8753-4-3 · Cited by 190 · see citing works
L1 retrotransposition can occur early in human embryonic development
van den Hurk, J. A. J. M., Meij, I. C., del Carmen Seleme, M., Kano, H., Nikopoulos, K., Hoefsloot, L. H., Sistermans, E. A., de Wijs, I. J., Mukhopadhyay, A., Plomp, A. S., et al. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm108 · Cited by 193 · see citing works
All y’all need to know ‘bout retroelements in cancer
Belancio, V. P., Roy‐Engel, A. M., & Deininger, P. L. (2010) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2010.06.001 · Cited by 189 · see citing works
A highly active synthetic mammalian retrotransposon
Han, J. S., & Boeke, J. D. (2004) · Nature · doi:10.1038/nature02535 · Cited by 181 · see citing works
Self-citationRibonucleoprotein particle formation is necessary but not sufficient for LINE-1 retrotransposition
Kulpa, D. A., & Moran, J. V. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi354 · Cited by 181 · see citing works
Genome surveillance by HUSH-mediated silencing of intronless mobile elements
Seczyńska, M., Bloor, S., Cuesta, S. M., & Lehner, P. J. (2021) · Nature · doi:10.1038/s41586-021-04228-1 · Cited by 180 · see citing works
An Arabidopsis hAT-like transposase is essential for plant development
Bundock, P., & Hooykaas, P. J. J. (2005) · Nature · doi:10.1038/nature03667 · Cited by 179 · see citing works
L1 Retrotransposons and Somatic Mosaicism in the Brain
Richardson, S. R., Morell, S., & Faulkner, G. J. (2014) · Annual Review of Genetics · doi:10.1146/annurev-genet-120213-092412 · Cited by 178 · see citing works
Environmental influence on L1 retrotransposons in the adult hippocampus
Muotri, A. R., Zhao, C., Marchetto, M. C., & Gage, F. H. (2009) · Hippocampus · doi:10.1002/hipo.20564 · Cited by 175 · see citing works
Host genome surveillance for retrotransposons by transposon-derived proteins
Cam, H. P., Noma, K.-I., Ebina, H., Levin, H. L., & Grewal, S. I. S. (2007) · Nature · doi:10.1038/nature06499 · Cited by 168 · see citing works
The Take and Give Between Retrotransposable Elements and their Hosts
Beauregard, A., Curcio, M. J., & Belfort, M. (2008) · Annual Review of Genetics · doi:10.1146/annurev.genet.42.110807.091549 · Cited by 168 · see citing works
Transposable elements in the mammalian embryo: pioneers surviving through stealth and service
Gerdes, P., Richardson, S. R., Mager, D. L., & Faulkner, G. J. (2016) · Genome biology · doi:10.1186/s13059-016-0965-5 · Cited by 163 · see citing works
ADAR Gene Family and A-to-I RNA Editing: Diverse Roles in Posttranscriptional Gene Regulation
Valente, L., & Nishikura, K. (2005) · Progress in nucleic acid research and molecular biology · doi:10.1016/s0079-6603(04)79006-6 · Cited by 168 · see citing works
Heteromeric RNP Assembly at LINEs Controls Lineage-Specific RNA Processing
Attig, J., Agostini, F., Gooding, C., Chakrabarti, A. M., Singh, A., Haberman, N., Zagalak, J. A., Emmett, W., Smith, C. W. J., Luscombe, N. M., et al. (2018) · Cell · doi:10.1016/j.cell.2018.07.001 · Cited by 166 · see citing works
Epigenetic regulation in mammalian preimplantation embryo development
Shi, L., & Wu, J. (2009) · Reproductive Biology and Endocrinology · doi:10.1186/1477-7827-7-59 · Cited by 163 · see citing works
Baba, Y., Huttenhower, C., Nosho, K., Tanaka, N., Shima, K., Hazra, A., Schernhammer, E. S., Hunter, D. J., Giovannucci, E. L., Fuchs, C. S., et al. (2010) · Molecular Cancer · doi:10.1186/1476-4598-9-125 · Cited by 161 · see citing works
Mammalian Small Nucleolar RNAs Are Mobile Genetic Elements
Weber, M. J. (2006) · PLoS Genetics · doi:10.1371/journal.pgen.0020205 · Cited by 159 · see citing works
L1Base 2: more retrotransposition-active LINE-1s, more mammalian genomes
Penzkofer, T., Jäger, M., Figlerowicz, M., Badge, R. M., Mundlos, S., Robinson, P. N., & Żemojtel, T. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw925 · Cited by 149 · see citing works
Dynamic DNA methylation: a prime candidate for genomic metaplasticity and behavioral adaptation
Baker‐Andresen, D., Ratnu, V. S., & Bredy, T. W. (2012) · Trends in Neurosciences · doi:10.1016/j.tins.2012.09.003 · Cited by 151 · see citing works
Response of transposable elements to environmental stressors
Miousse, I. R., Chalbot, M. G., Lumen, A., Ferguson, A., Kavouras, I. G., & Koturbash, I. (2015) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2015.05.003 · Cited by 144 · see citing works
LINE dancing in the human genome: transposable elements and disease
Belancio, V. P., Deininger, P. L., & Roy-Engel, A. M. (2009) · Genome Medicine · doi:10.1186/gm97 · Cited by 146 · see citing works
Long interspersed nuclear element-1 hypomethylation in cancer: biology and clinical applications
Kitkumthorn, N., & Mutirangura, A. (2011) · Clinical Epigenetics · doi:10.1007/s13148-011-0032-8 · Cited by 142 · see citing works
Retroelements and their impact on genome evolution and functioning
Gogvadze, E. V., & Buzdin, A. A. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-0107-2 · Cited by 141 · see citing works
Gamma radiation increases endonuclease-dependent L1 retrotransposition in a cultured cell assay
Farkash, E. A. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkj522 · Cited by 141 · see citing works
Expression of LINE-1 retroposons is essential for murine preimplantation development
Beraldi, R., Pittoggi, C., Sciamanna, I., Mattei, E., & Spadafora, C. (2005) · Molecular Reproduction and Development · doi:10.1002/mrd.20423 · Cited by 139 · see citing works
Retroelements in human disease
Kaer, K., & Speek, M. (2013) · Gene · doi:10.1016/j.gene.2013.01.008 · Cited by 140 · see citing works
LINE-1 hypomethylation level as a potential prognostic factor for epithelial ovarian cancer
Pattamadilok, J., Huapai, N., Rattanatanyong, P., Vasurattana, A., Triratanachat, S., Tresukosol, D., & Mutirangura, A. (2007) · International Journal of Gynecological Cancer · doi:10.1111/j.1525-1438.2007.01117.x · Cited by 140 · see citing works
Sleeping beauty transposon-mediated gene therapy for prolonged expression.
Hackett, P. B., Ekker, S. C., Largaespada, D., & McIvor, R. (2005) · Advances in Genetics · doi:10.1016/s0065-2660(05)54009-4 · Cited by 136 · see citing works
Gene-breaking: A new paradigm for human retrotransposon-mediated gene evolutionPreprint
Wheelan, S. J., Aizawa, Y., Han, J. S., & Boeke, J. D. (2005) · Genome Research · doi:10.1101/gr.3688905 · Cited by 129 · see citing works
Self-citationGenome-wide de novo L1 Retrotransposition Connects Endonuclease Activity with Replication
Flasch, D. A., Macia, Á., Sánchez, L., Ljungman, M., Heras, S. R., García-Pérez, J. L., Wilson, T. E., & Moran, J. V. (2019) · Cell · doi:10.1016/j.cell.2019.02.050 · Cited by 127 · see citing works
Jung‐Klawitter, S., Fuchs, N. V., Upton, K. R., Muñoz-López, M., Shukla, R., Wang, J., García-Cañadas, M., Lopez‐Ruiz, C., Gerhardt, D. J., Sebe, A., et al. (2016) · Nature Communications · doi:10.1038/ncomms10286 · Cited by 124 · see citing works
Short interspersed elements (SINEs) are a major source of canine genomic diversityPreprint
Wang, W., & Kirkness, E. F. (2005) · Genome Research · doi:10.1101/gr.3765505 · Cited by 125 · see citing works
Lee, J. Y., Ji, Z., & Tian, B. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn540 · Cited by 125 · see citing works
Epigenetic regulation of the rice retrotransposon Tos17
Cheng, C., Daigen, M., & Hirochika, H. (2006) · Molecular Genetics and Genomics · doi:10.1007/s00438-006-0141-9 · Cited by 123 · see citing works
Baccarelli, A., Tarantini, L., Wright, R. O., Bollati, V., Litonjua, A. A., Zanobetti, A., Sparrow, D., Vokonas, P., & Schwartz, J. D. (2010) · Epigenetics · doi:10.4161/epi.5.3.11377 · Cited by 122 · see citing works
LINE-1 in cancer: multifaceted functions and potential clinical implications
Lu, X., Hui-Ying, X., Qi, X., Jiang, X., & Ma, S. (2015) · Genetics in Medicine · doi:10.1038/gim.2015.119 · Cited by 121 · see citing works
Hiratani, I., Leskovar, A., & Gilbert, D. M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406687101 · Cited by 116 · see citing works
Active retrotransposition by a synthetic L1 element in mice
An, W., Han, J. S., Wheelan, S. J., Davis, E. S., Coombes, C. E., Ye, P., Triplett, C., & Boeke, J. D. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605300103 · Cited by 117 · see citing works
Self-citationPrenatal maternal immune activation causes epigenetic differences in adolescent mouse brain
Basil, P., Li, Q., Dempster, E. L., Mill, J., Sham, P.-C., Wong, C. C. Y., & McAlonan, G. M. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.80 · Cited by 116 · see citing works
Heritable L1 retrotransposition in the mouse primordial germline and early embryoPreprint
Richardson, S. R., Gerdes, P., Gerhardt, D. J., Sanchez-Luque, F. J., Bodea, G. O., Muñoz-López, M., Jesuadian, J. S., Kempen, M.-J. H. C., Carreira, P. E., Jeddeloh, J. A., et al. (2017) · Genome Research · doi:10.1101/gr.219022.116 · Cited by 114 · see citing works
L1 Mosaicism in Mammals: Extent, Effects, and Evolution
Faulkner, G. J., & Garcia-Perez, J. L. (2017) · Trends in Genetics · doi:10.1016/j.tig.2017.07.004 · Cited by 110 · see citing works
Exon-trapping mediated by the human retrotransposon SVAPreprint
Hancks, D. C., Ewing, A. D., Chen, J. E., Tokunaga, K., & Kazazian, H. H. (2009) · Genome Research · doi:10.1101/gr.093153.109 · Cited by 111 · see citing works
Complex patterns of transcription at the insertion site of a retrotransposon in the mouse
Druker, R. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh914 · Cited by 110 · see citing works
L1Base: from functional annotation to prediction of active LINE-1 elements
Penzkofer, T. (2004) · Nucleic Acids Research · doi:10.1093/nar/gki044 · Cited by 108 · see citing works
- Authors
- Han, J. S., Szak, S. T., & Boeke, J. D.
- Affiliations
- Johns Hopkins University (US)
- Biogen (United States) (US)
- Corresponding author
- Boeke, Jef D.
- Venue
- Nature
- Published
- 2004-05
- Volume
- 429
- Issue
- 6989
- Pages
- 268-274
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1981262837
- Cited by
- 484
- References
- 52
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 12 · 2023: 18 · 2022: 13 · 2021: 24 · 2020: 18 · 2019: 12 · 2018: 21 · 2017: 21 · 2016: 22 · 2015: 15 · 2014: 22 · 2013: 25 · 2012: 34
- FWCI
- 48.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- LINE-1 retrotransposons, transcription elongation, ORF1, retrotransposon expression, gene expression regulation, human transcriptome, transposable elements, RNA stability, transcription initiation
- MeSH terms
- Animals, Base Sequence, Cell Line, Endonucleases, Half-Life, Humans, Mammals, Models, Genetic, RNA-Directed DNA Polymerase, RNA Polymerase III, RNA, Messenger, Transcription, Genetic, Down-Regulation, Open Reading Frames, Evolution, Molecular, Computational Biology, Long Interspersed Nucleotide Elements, RNA Stability, Feedback, Physiological, Mice
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