Genomes and Genes
long interspersed nucleotide elements
Summary: Highly repeated sequences, 6K-8K base pairs in length, which contain RNA polymerase II promoters. They also have an open reading frame that is related to the reverse transcriptase of retroviruses but they do not contain LTRs (long terminal repeats). Copies of the LINE 1 (L1) family form about 15% of the human genome. The jockey elements of Drosophila are LINEs.
- Vitullo P, Sciamanna I, Baiocchi M, Sinibaldi Vallebona P, Spadafora C. LINE-1 retrotransposon copies are amplified during murine early embryo development. Mol Reprod Dev. 2012;79:118-27 pubmed publisher..These findings support the conclusion that RT-dependent amplification of LINE-1 retrotransposons is a distinctive feature of early embryonic genomes. Its physiological involvement in preimplantation murine development is discussed. ..
- Iwagami S, Baba Y, Watanabe M, Shigaki H, Miyake K, Ida S, et al. Pyrosequencing assay to measure LINE-1 methylation level in esophageal squamous cell carcinoma. Ann Surg Oncol. 2012;19:2726-32 pubmed publisher..The aim of this study is to assess the precision of sodium bisulfite conversion and polymerase chain reaction (PCR) pyrosequencing assay for evaluating LINE-1 methylation in ESCC...
- Wolff E, Byun H, Han H, Sharma S, Nichols P, Siegmund K, et al. Hypomethylation of a LINE-1 promoter activates an alternate transcript of the MET oncogene in bladders with cancer. PLoS Genet. 2010;6:e1000917 pubmed publisher..These data show that, in addition to contributing to chromosomal instability, hypomethylation of LINE-1s can alter the functional transcriptome and plays a role not only in human disease but also in disease predisposition. ..
- Li X, Zhang J, Jia R, Cheng V, Xu X, Qiao W, et al. The MOV10 helicase inhibits LINE-1 mobility. J Biol Chem. 2013;288:21148-60 pubmed publisher..These data demonstrate collectively that MOV10 contributes to the cellular control of LINE-1 replication. ..
- Solyom S, Ewing A, Rahrmann E, Doucet T, Nelson H, Burns M, et al. Extensive somatic L1 retrotransposition in colorectal tumors. Genome Res. 2012;22:2328-38 pubmed publisher..Numerous genes with a role in tumorigenesis were targeted, including ODZ3, ROBO2, PTPRM, PCM1, and CDH11. Thus, somatic retrotransposition may play an etiologic role in colorectal cancer. ..
- Shukla R, Upton K, Muñoz Lopez M, Gerhardt D, Fisher M, Nguyen T, et al. Endogenous retrotransposition activates oncogenic pathways in hepatocellular carcinoma. Cell. 2013;153:101-11 pubmed publisher..These proof-of-principle results substantiate L1-mediated retrotransposition as an important etiological factor in HCC. ..
- Irahara N, Nosho K, Baba Y, Shima K, Lindeman N, Hazra A, et al. Precision of pyrosequencing assay to measure LINE-1 methylation in colon cancer, normal colonic mucosa, and peripheral blood cells. J Mol Diagn. 2010;12:177-83 pubmed publisher..9) in leukocyte DNA. In conclusion, bisulfite conversion and PCR-pyrosequencing assay can measure LINE-1 methylation in macrodissected colon cancer, normal colon, and blood DNA, and may be useful in clinical and research settings...
- Wagstaff B, Hedges D, Derbes R, Campos Sanchez R, Chiaromonte F, Makova K, et al. Rescuing Alu: recovery of new inserts shows LINE-1 preserves Alu activity through A-tail expansion. PLoS Genet. 2012;8:e1002842 pubmed publisher..We postulate that the A-tail expansion directly impacts Alu evolution by reintroducing new active source elements to counteract the natural loss of active Alus and minimizing Alu extinction. ..
- Shigaki H, Baba Y, Watanabe M, Murata A, Iwagami S, Miyake K, et al. LINE-1 hypomethylation in gastric cancer, detected by bisulfite pyrosequencing, is associated with poor prognosis. Gastric Cancer. 2013;16:480-7 pubmed publisher..25). LINE-1 hypomethylation in gastric cancer is associated with shorter survival, suggesting that it has potential for use as a prognostic biomarker. ..
- Singer H, Walier M, Nüsgen N, Meesters C, Schreiner F, Woelfle J, et al. Methylation of L1Hs promoters is lower on the inactive X, has a tendency of being higher on autosomes in smaller genomes and shows inter-individual variability at some loci. Hum Mol Genet. 2012;21:219-35 pubmed publisher..In summary, loci-specific LINE-1 methylation levels show considerable plasticity and depend on genomic position and constitution. ..
- Murata A, Baba Y, Watanabe M, Shigaki H, Miyake K, Ishimoto T, et al. Methylation levels of LINE-1 in primary lesion and matched metastatic lesions of colorectal cancer. Br J Cancer. 2013;109:408-15 pubmed publisher..Alteration of LINE-1 methylation level may occur in early CRC tumorigenesis, and the LINE-1 methylation level is relatively stable during CRC progression. ..
- Sigalotti L, Fratta E, Bidoli E, Covre A, Parisi G, Colizzi F, et al. Methylation levels of the "long interspersed nucleotide element-1" repetitive sequences predict survival of melanoma patients. J Transl Med. 2011;9:78 pubmed publisher..01). LINE-1 methylation is identified as a molecular marker of prognosis for CM patients in stage IIIC. Evaluation of LINE-1 promises to represent a key tool for driving the most appropriate clinical management of stage III CM patients. ..
- Fadloun A, Le Gras S, Jost B, Ziegler Birling C, Takahashi H, Gorab E, et al. Chromatin signatures and retrotransposon profiling in mouse embryos reveal regulation of LINE-1 by RNA. Nat Struct Mol Biol. 2013;20:332-8 pubmed publisher..Our data indicate that reprogramming after mammalian fertilization comprises a robust transcriptional activation of retrotransposons and that repetitive elements are initially regulated through RNA. ..
- Wissing S, Montano M, Garcia Perez J, Moran J, Greene W. Endogenous APOBEC3B restricts LINE-1 retrotransposition in transformed cells and human embryonic stem cells. J Biol Chem. 2011;286:36427-37 pubmed publisher..Knockdown of the other A3s produced no significant increase in L1 activity. Thus, A3B appears to restrict engineered L1 retrotransposition in a broad range of cell types, including pluripotent cells. ..
- Peddigari S, Li P, Rabe J, Martin S. hnRNPL and nucleolin bind LINE-1 RNA and function as host factors to modulate retrotransposition. Nucleic Acids Res. 2013;41:575-85 pubmed publisher..Thus, hnRNPL joins a small, but growing list of cellular proteins that are potent negative regulators of L1 retrotransposition. ..
- Solyom S, Ewing A, Hancks D, Takeshima Y, Awano H, Matsuo M, et al. Pathogenic orphan transduction created by a nonreference LINE-1 retrotransposon. Hum Mutat. 2012;33:369-71 pubmed publisher..Thus, the likely explanation for the mutagenic insertion is a LINE-1-mediated 3' transduction with severe 5' truncation. This is the first example of LINE-1-induced human disease caused by an "orphan" 3' transduction. ..
- Han J, Shao S. Circular retrotransposition products generated by a LINE retrotransposon. Nucleic Acids Res. 2012;40:10866-77 pubmed publisher..These episomal products are a previously unseen alternative fate of LINE retrotransposition, and may represent an unexpected source for de novo retrotransposition. ..
- Newman M, Blyth B, Hussey D, Jardine D, Sykes P, Ormsby R. Sensitive quantitative analysis of murine LINE1 DNA methylation using high resolution melt analysis. Epigenetics. 2012;7:92-105 pubmed publisher..The L1 assay provides a high throughput, inexpensive and sensitive screening tool for identifying and characterizing DNA methylation changes to L1 elements at multiple regions across the genome. ..
- Banaz Yaşar F, Gedik N, Karahan S, Díaz Carballo D, Bongartz B, Ergun S. LINE-1 retrotransposition events regulate gene expression after X-ray irradiation. DNA Cell Biol. 2012;31:1458-67 pubmed publisher..Taken together, our findings provide that LINE-1 retrotransposition events regulate different gene expression after irradiation in the EA.hy926 cell line. ..
- Cash H, Tao L, Yuan J, Marsit C, Houseman E, Xiang Y, et al. LINE-1 hypomethylation is associated with bladder cancer risk among nonsmoking Chinese. Int J Cancer. 2012;130:1151-9 pubmed publisher..006). Further research is needed to understand the relationships between methyl group availability and LINE-1 methylation in relation to bladder cancer risk. ..
- Madrigano J, Baccarelli A, Mittleman M, Wright R, Sparrow D, Vokonas P, et al. Prolonged exposure to particulate pollution, genes associated with glutathione pathways, and DNA methylation in a cohort of older men. Environ Health Perspect. 2011;119:977-82 pubmed publisher..The glutathione S-transferase mu-1-null genotype strengthened the association between BC and Alu hypomethylation. Prolonged exposure to BC and SO? particles was associated with hypomethylation of two types of repetitive elements. ..
- Crow M. Long interspersed nuclear elements (LINE-1): potential triggers of systemic autoimmune disease. Autoimmunity. 2010;43:7-16 pubmed publisher..Induction of type I IFN by L1-enriched nucleic acids through TLR-independent pathways could represent a first step in the complex series of events leading to systemic autoimmune disease. ..
- Iramaneerat K, Rattanatunyong P, Khemapech N, Triratanachat S, Mutirangura A. HERV-K hypomethylation in ovarian clear cell carcinoma is associated with a poor prognosis and platinum resistance. Int J Gynecol Cancer. 2011;21:51-7 pubmed publisher..The expressions of human endogenous retrovirus (HERV) K and E were found to be increased in tissues from patients with OCCC. Here, we propose that methylation levels of HERV are associated with treatment response and prognosis of OCCC...
- Morisada N, Rendtorff N, Nozu K, Morishita T, Miyakawa T, Matsumoto T, et al. Branchio-oto-renal syndrome caused by partial EYA1 deletion due to LINE-1 insertion. Pediatr Nephrol. 2010;25:1343-8 pubmed publisher..Although there are reports of L1 element insertion occurring in various human diseases, this is the first report of a large EYA1 deletion in combination with L1 element insertion. ..
- Pobsook T, Subbalekha K, Sannikorn P, Mutirangura A. Improved measurement of LINE-1 sequence methylation for cancer detection. Clin Chim Acta. 2011;412:314-21 pubmed publisher..0082 and p=0.4830, respectively). LINE-1 partial methylation represents hypomethylation in normal cells but hypermethylation in cancer cells. This information improves LINE-1 methylation detection in cancer. ..
- Khatua A, Taylor H, Hildreth J, Popik W. Inhibition of LINE-1 and Alu retrotransposition by exosomes encapsidating APOBEC3G and APOBEC3F. Virology. 2010;400:68-75 pubmed publisher..A3G mRNA, and less so A3F, was enriched in exosomes secreted by H9 cells. Exosomal A3G mRNA was functional in vitro. Whether exosomes inhibit retrotransposons in vivo requires further investigation. ..
- Baba Y, Huttenhower C, Nosho K, Tanaka N, Shima K, Hazra A, et al. Epigenomic diversity of colorectal cancer indicated by LINE-1 methylation in a database of 869 tumors. Mol Cancer. 2010;9:125 pubmed publisher..Our tumor LINE-1 methylation data indicate enormous epigenomic diversity of individual colorectal cancers. ..
- Rangasamy D. An S/MAR-based L1 retrotransposition cassette mediates sustained levels of insertional mutagenesis without suffering from epigenetic silencing of DNA methylation. Epigenetics. 2010;5:601-11 pubmed
- Singer T, McConnell M, Marchetto M, Coufal N, Gage F. LINE-1 retrotransposons: mediators of somatic variation in neuronal genomes?. Trends Neurosci. 2010;33:345-54 pubmed publisher..We discuss potential consequences of L1-induced neuronal diversity and propose that a mechanism for generating diversity in the brain could broaden the spectrum of behavioral phenotypes that can originate from any single genome. ..
- Kvikstad E, Makova K. The (r)evolution of SINE versus LINE distributions in primate genomes: sex chromosomes are important. Genome Res. 2010;20:600-13 pubmed publisher..Thus, Alu and L1 densities have been influenced by the combination of distinct local genome landscapes and the unique evolutionary dynamics of sex chromosomes...
- Belancio V, Roy Engel A, Pochampally R, Deininger P. Somatic expression of LINE-1 elements in human tissues. Nucleic Acids Res. 2010;38:3909-22 pubmed publisher..These findings have potential consequences for the whole organism in the form of cancer and mammalian aging. ..
- Wilhelm C, Kelsey K, Butler R, Plaza S, Gagne L, Zens M, et al. Implications of LINE1 methylation for bladder cancer risk in women. Clin Cancer Res. 2010;16:1682-9 pubmed publisher..04), and levels of arsenic in the 90th percentile were associated with reduced LINE1 methylation (P = 0.04). LINE1 hypomethylation may be an important biomarker of bladder cancer risk, especially among women. ..
- Rosser J, An W. Repeat-induced gene silencing of L1 transgenes is correlated with differential promoter methylation. Gene. 2010;456:15-23 pubmed publisher..In summary, our data suggest that tandem arrayed L1 transgenes are subject to RIGS, and transgenes present at a single copy in the genome are thus recommended for modeling L1 in animals. ..
- Jintaridth P, Mutirangura A. Distinctive patterns of age-dependent hypomethylation in interspersed repetitive sequences. Physiol Genomics. 2010;41:194-200 pubmed publisher..However, not all of these mechanisms are age-dependent. This finding may lead to a better understanding of not only the biological causes and consequences of genome-wide hypomethylation but also the role of IRSs in the aging process. ..
- Booth M, Branco M, Ficz G, Oxley D, Krueger F, Reik W, et al. Quantitative sequencing of 5-methylcytosine and 5-hydroxymethylcytosine at single-base resolution. Science. 2012;336:934-7 pubmed publisher..Our results open new questions on 5hmC dynamics and sequence-specific targeting by TETs...
- Kitkumthorn N, Tuangsintanakul T, Rattanatanyong P, Tiwawech D, Mutirangura A. LINE-1 methylation in the peripheral blood mononuclear cells of cancer patients. Clin Chim Acta. 2012;413:869-74 pubmed publisher..Changes in the levels and patterns of genome-wide methylation of PBMCs are associated with cancer risk. For LINE-1, %(u)C(u)C is a more effective tumour marker for determining cancer risk than overall methylation levels. ..
- Garcia Perez J, Morell M, Scheys J, Kulpa D, Morell S, Carter C, et al. Epigenetic silencing of engineered L1 retrotransposition events in human embryonic carcinoma cells. Nature. 2010;466:769-73 pubmed publisher..Thus, our data indicate that ECs differ from many differentiated cells in their ability to silence reporter genes delivered by L1 retrotransposition. ..
- Bae J, Shin S, Kwon H, Park S, Kook M, Kim Y, et al. ALU and LINE-1 hypomethylations in multistep gastric carcinogenesis and their prognostic implications. Int J Cancer. 2012;131:1323-31 pubmed publisher..Furthermore, the LINE-1 methylation status can be used as a molecular biomarker to define a subset of GC patients with poor prognosis. ..
- Okudaira N, Iijima K, Koyama T, Minemoto Y, Kano S, Mimori A, et al. Induction of long interspersed nucleotide element-1 (L1) retrotransposition by 6-formylindolo[3,2-b]carbazole (FICZ), a tryptophan photoproduct. Proc Natl Acad Sci U S A. 2010;107:18487-92 pubmed publisher..A possible role of ARNT1-mediated L1-RTP in the adaptation of living organisms to environmental changes is discussed. ..
- Ichiyanagi K, Li Y, Li Y, Watanabe T, Ichiyanagi T, Fukuda K, et al. Locus- and domain-dependent control of DNA methylation at mouse B1 retrotransposons during male germ cell development. Genome Res. 2011;21:2058-66 pubmed publisher..Taken altogether, our results not only reveal the dynamics and mode of SINE methylation but also suggest how the DNA methylation profile is created in the germline by a pair of DNA methyltransferases. ..
- De Fazio S, Bartonicek N, Di Giacomo M, Abreu Goodger C, Sankar A, Funaya C, et al. The endonuclease activity of Mili fuels piRNA amplification that silences LINE1 elements. Nature. 2011;480:259-63 pubmed publisher..In addition, the hallmarks of piRNA amplification are observed in Miwi2-deficient gonadocytes. We conclude that cycles of intra-Mili secondary piRNA biogenesis fuel piRNA amplification that is absolutely required for LINE1 silencing. ..
- Muotri A, Marchetto M, Coufal N, Oefner R, Yeo G, Nakashima K, et al. L1 retrotransposition in neurons is modulated by MeCP2. Nature. 2010;468:443-6 pubmed publisher..Our findings add a new level of complexity to the molecular events that can lead to neurological disorders...
- Ting D, Lipson D, Paul S, Brannigan B, Akhavanfard S, Coffman E, et al. Aberrant overexpression of satellite repeats in pancreatic and other epithelial cancers. Science. 2011;331:593-6 pubmed publisher..The overexpression of satellite transcripts in cancer may reflect global alterations in heterochromatin silencing and could potentially be useful as a biomarker for cancer detection. ..
- Zhang F, Cardarelli R, CARROLL J, Fulda K, Kaur M, Gonzalez K, et al. Significant differences in global genomic DNA methylation by gender and race/ethnicity in peripheral blood. Epigenetics. 2011;6:623-9 pubmed..Global leukocyte DNA methylation differs by gender and race/ethnicity, suggesting these variables need to be taken into consideration in studies of global DNA methylation as an epigenetic marker for cancer. ..
- Nelson H, Marsit C, Kelsey K. Global methylation in exposure biology and translational medical science. Environ Health Perspect. 2011;119:1528-33 pubmed publisher..Among the most urgent avenues of research is the need for prospective studies to eliminate the possibilities of reverse causality, and development of new LINE-1 assays that capture both class of LINE-1 element and copy number. ..
- Ikeda T, Abd El Galil K, Tokunaga K, Maeda K, Sata T, Sakaguchi N, et al. Intrinsic restriction activity by apolipoprotein B mRNA editing enzyme APOBEC1 against the mobility of autonomous retrotransposons. Nucleic Acids Res. 2011;39:5538-54 pubmed publisher..Thus, the AID/APOBEC family proteins including A1s employ multiple mechanisms to regulate the mobility of autonomous retrotransposons in several mammalian species. ..