リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「Effects of transgene insertion locus and copy number on endogenous Dnmt3L gene silencing by antisense transgene derived piRNAs」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

Effects of transgene insertion locus and copy number on endogenous Dnmt3L gene silencing by antisense transgene derived piRNAs

李, 世弼 大阪大学 DOI:10.18910/85274

2021.06.15

概要

PIWI-interacting RNA (piRNA) is a class of small RNAs regulated by PIWI (Argonaute subfamily), which are abundantly expressed in germline cells. piRNAs contribute to both post-transcriptional gene silencing (PTGS) and methylation-mediated transcriptional gene silencing (TGS). These piRNAs are synthesized from sense and anti-sense RNA containing transposable elements transcribed from piRNA clusters, and piRNAmediated silencing of retrotransposon genes is essential for spermatogenesis progression. In a previous study, we found that the sole occurrence of sense and anti-sense RNA against a specific gene is sufficient to mimic the natural piRNA system. Namely, Miwi2 promoter-driven anti-sense Dnmt3L-expressing transgenic mice (Tg-Miwi2p-asDnmt3L) exhibited a DNMT3L-deficient phenotype caused by piRNA mediated epigenetic silencing in the embryonic germ cells. However, It was not determined whether the production of Dnmt3L piRNA was derived from the Miwi2 promoter-driven transgene or from a transgene inserted onto the piRNA cluster. Therefore, whole-genome sequencing was conducted to clarify the transgene insertion loci. Two transgene insertion loci (18qB3 and 18qE1) were identified on chromosome 18 in Tg-asDnmt3L mice, and both were recognized as weak piRNA clusters. Mice that exclusively carried transgenes in a single locus were then isolated via crossbreeding. DNMT3L was silenced and spermatogenesis was severely impaired in the mice carrying the transgene at the 18qB3 locus (B3). In contrast, the spermatogenesis of the mice bearing the transgene at the 18qE1 locus (E1) was normal. Small RNA-seq data revealed that the number of piRNA corresponding to Dnmt3L were higher in the B3 than in the E1. Additionally, the B3 exhibited high copy numbers of the transgene, whereas the opposite was true for the E1. Moreover, the endogenous Dnmt3L promoter was not methylated in the studied Tg mice. Taken together, these findings indicate that artificial piRNA-mediated Dnmt3L silencing was caused by PTGS and was more dependent on transgene copy number rather than transgene insertion locus.

この論文で使われている画像

参考文献

1. Aravin A, Gaidatzis D, Pfeffer S, Lagos-Quintana M, Landgraf P, Iovino N, Morris P, Brownstein MJ, KuramochiMiyagawa S, Nakano T, Chien M, Russo JJ, Ju J, Sheridan R, Sander C, Zavolan M, Tuschl T. A novel class of small RNAs bind to MILI protein in mouse testes. Nature 442, 203–207 (2006).

2. Aravin, A. A., Sachidanandam, R., Girard, A., Fejes-Toth, K. & Hannon, G. J. Developmentally regulated piRNA clusters implicate MILI in transposon control. Science 316, 744–747 (2007).

3. Aravin A.A, Sachidanandam R, Bourc'his D, Schaefer C, Pezic D, Toth KF, Bestor T, Hannon GJ. A piRNA pathway primed by individual transposons is linked to De novo DNA methylation in mice. Mol. Cell 31, 785– 799 (2008).

4. Abrusán G, Grundmann N, DeMester L, Makalowski W. TEclass-a tool for automated classification of unknown eukaryotic transposable elements. Bioinformatics. 15;25(10):1329-30. (2009)

5. Ayarpadikannan, S., & Kim, H. S. The impact of transposable elements in genome evolution and genetic instability and their implications in various diseases. Genomics & informatics, 12(3), 98–104. (2014)

6. Bourc’his, D. & Bestor, T. H. Meiotic catastrophe and retrotransposon reactivation in male germ cells lacking Dnmt3L. Nature 431, 96–99 (2004).

7. Babushok, D. V, Kazazian, H.H., and Jr, Ã. Progress in understanding the biology of the human mutagen LINE-1. Hum. Mutat. 28, 527–539. (2007)

8. Julius Brennecke, Alexei A Aravin, Alexander Stark, Monica Dus, Manolis Kellis, Ravi Sachidanandam, Gregory J Hannon Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila. Cell. ;128(6):1089-103. (2007)

9. Chinwalla, A. et al., Mouse Genome Sequencing Consortium., Genome Sequencing Center Initial sequencing and comparative analysis of the mouse genome. Nature 420, 520–562 (2002).

10. Carmell, M.A., Girard, A., van de Kant, H.J., Bourc'his, D., Bestor, T.H., de Rooij, D.G., and Hannon, G.J. MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline. Dev Cell 12, 503-514 (2007).

11. Dewannieux M, Heidmann T. Role of poly(A) tail length in Alu retrotransposition. Genomics. 86(3):378-81. (2005)

12. Esnault, C., Maestre, J., and Heidmann, T. Human LINE retrotransposons generate processed pseudogenes. Nat. Genet. 24, 363–367. (2000)

13. Ernst, C., Odom, D.T. & Kutter, C. The emergence of piRNAs against transposon invasion to preserve mammalian genome integrity. Nat Commun 8, 1411 (2017).

14. De Fazio S, Bartonicek N, Di Giacomo M, Abreu-Goodger C, Sankar A, Funaya C, Antony C, Moreira PN, Enright AJ, O'Carroll D. The endonuclease activity of Mili fuels piRNA amplification that silences LINE1 elements. Nature 480, 259–263 (2011).

15. Girard, A., Sachidanandam, R., Hannon, G.J., and Carmell, M.A. A germline-specific class of small RNAs binds mammalian Piwi proteins.Nature 442, 199-202 (2006).

16. Monica Di Giacomo, Stefano Comazzetto, Harpreet Saini, Serena De Fazio, Claudia Carrieri, Marcos Morgan, Lina Vasiliauskaite, Vladimir Benes, Anton J. Enright, and Do´ nal O’Carroll Multiple epigenetic mechanisms and the piRNA pathway enforce LINE1 silencing during adult spermatogenesis. Mol. Cell 50, 601–608 (2013).

17. Grechishnikova D, Poptsova M. Conserved 3' UTR stem-loop structure in L1 and Alu transposons in human genome: possible role in retrotransposition. BMC Genomics. 3;17(1):992. (2016)

18. Gainetdinov I, Colpan C, Arif A, Cecchini K, Zamore PD. A Single Mechanism of Biogenesis, Initiated and Directed by PIWI Proteins, Explains piRNA Production in Most Animals. Mol Cell. 71(5):775-790.e5. (2018)

19. Gagnier, L., Belancio, V.P. & Mager, D.L. Mouse germ line mutations due to retrotransposon insertions. Mobile DNA 10, 15 (2019).

20. Hajkova P, Erhardt S, Lane N, Haaf T, El-Maarri O, Reik W, Walter J, Surani MA. Epigenetic reprogramming in mouse primordial germ cells. Mech. Dev. 117, 15–23 (2002).

21. Ipsaro, J. J., Haase, A. D., Knott, S. R., Joshua-Tor, L. & Hannon, G. J. The structural biochemistry of Zucchini implicates it as a nuclease in piRNA biogenesis. Nature 491, 279–283 (2012).

22. Itou D, Shiromoto Y, Yukiho SY, Ishii C, Nishimura T, Ogonuki N, Ogura A, Hasuwa H, Fujihara Y, KuramochiMiyagawa S, Nakano T. Induction of DNA methylation by artificial piRNA production in male germ cells. Curr. Biol. 25, 901–906 (2015).

23. Kajikawa, M., and Okada, N. LINEs Mobilize SINEs in the Eel through a Shared 3′ Sequence. Cell 111, 433–444. (2002).

24. Masahiro Kaneda, Masaki Okano3,4, Kenichiro Hata, Takashi Sado, Naomi Tsujimoto, En Li & Hiroyuki SasakiEssential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting. Nature, 429(6994):900-3. (2004)

25. Kramerov, D.A., and Vassetzky, N.S. Origin and evolution of SINEs in eukaryotic genomes. Heredity (Edinb). 107, 487–495. (2011)

26. Kato Y, Kaneda M, Hata K, Kumaki K, Hisano M, Kohara Y, Okano M, Li E, Nozaki M, Sasaki H. Role of the Dnmt3 family in De novo methylation of imprinted and repetitive sequences during male germ cell development in the mouse. Hum. Mol. Genet. 16, 2272–2280 (2007).

27. Kanako Kojima-Kita, Satomi Kuramochi-Miyagawa, Ippei Nagamori, Narumi Ogonuki, Atsuo Ogura, Hidetoshi Hasuwa, Takashi Akazawa, orimitsu Inoue, Toru Nakano MIWI2 as an Effector of DNA Methylation and Gene Silencing in Embryonic Male Germ Cells. Cell Rep 16, 11, 2819- 2828 (2016)

28. Lee J, Inoue K, Ono R, Ogonuki N, Kohda T, Kaneko-Ishino T, Ogura A, Ishino F. Erasing genomic imprinting memory in mouse clone embryos produced from day 11.5 primordial germ cells. Development 129, 1807–1817 (2002).

29. Li, J. Y., Lees-Murdock, D. J., Xu, G. L. & Walsh, C. P. Timing of establishment of paternal methylation imprints in the mouse. Genomics 84, 952–960 (2004).

30. Li, J., Kannan, M., Trivett, A.L., Liao, H., Wu, X., Akagi, K., and Symer, D.E. An antisense promoter in mouse L1 retrotransposon open reading frame-1 initiates expression of diverse fusion transcripts and limits retrotransposition. Nucleic Acids Res. 42, 4546–4562. (2014)

31. Lam JK, Chow MY, Zhang Y, Leung SW. siRNA Versus miRNA as Therapeutics for Gene Silencing. Mol Ther Nucleic Acids. 15;4(9):e252. (2015)

32. Han Li C, Chen Y. Small and Long Non-Coding RNAs: Novel Targets in Perspective Cancer Therapy. Curr Genomics. 2015;16(5):319-326. (2015)

33. Lim SL, Qu ZP, Kortschak RD, Lawrence DM, Geoghegan J, Hempfling AL, Bergmann M, Goodnow CC, Ormandy CJ, Wong L, Mann J, Scott HS, Jamsai D, Adelson DL, O'Bryan MK. HENMT1 and piRNA stability are required for adult male germ cell transposon repression and to define the spermatogenic program in the mouse. PLoS Genet. 11, e1005620 (2015).

34. Martin, S.L., and Bushman, F.D. Nucleic acid chaperone activity of the ORF1 protein from the mouse LINE-1 retrotransposon. Mol. Cell. Biol. 21, 467– 475. 2001)

35. Satomi Kuramochi-Miyagawa, Tohru Kimura, Kentaro Yomogida, Asato Kuroiwa, Yuko Tadokoro, Yukiko Fujita, Masatake Sato, Yoichi Matsuda, Toru Nakano Two mouse piwi-related genes: miwi and mili. Mech Dev 108 121–133 (2001)

36. Kuramochi-Miyagawa S, Kimura T, Ijiri TW, Isobe T, Asada N, Fujita Y, Ikawa M, Iwai N, Okabe M, Deng W, Lin H, Matsuda Y, Nakano T. Mili, a mammalian member of piwi family gene, is essential for spermatogenesis. Dev. Camb. Engl. 131, 839–849 (2004).

37. Morris, K. V., Chan, S. W., Jacobsen, S. E. & Looney, D. J. Small interfering RNA-induced transcriptional gene silencing in human cells. Science 305, 1289–1292 (2004).

38. Martin, S.L., Cruceanu, M., Branciforte, D., Wai-Lun Li, P., Kwok, S.C., Hodges, R.S., and Williams, M.C. LINE-1 retrotransposition requires the nucleic acid chaperone activity of the ORF1 protein. J. Mol. Biol. 348, 549–561. (2005)

39. Satomi Kuramochi-Miyagawa, Toshiaki Watanabe, Kengo Gotoh, Yasushi Totoki, Atsushi Toyoda, Masahito Ikawa, Noriko Asada, Kanako Kojima, Yuka Yamaguchi, Takashi W. Ijiri, Kenichiro Hata, En Li, Yoichi Matsuda, Tohru Kimura, Masaru Okabe, Yoshiyuki Sakaki, Hiroyuki Sasaki, Toru Nakano DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes. Genes & Dev. 22: 908-917 (2008)

40. Shinpei Kawaoka, Hiroshi Mitsutake, Takashi Kiuchi,1 Maki Kobayashi, Mayu Yoshikawa, Yutaka Suzuki, Sumio Sugano, Toru Shimada, Jun Kobayashi, Yukihide Tomari, and Susumu Katsuma A role for transcription from a piRNA cluster in de novo piRNA production. RNA. Feb; 18(2): 265–273 (2012)

41. Antoine Molaro, Ilaria Falciatori, Emily Hodges, Alexei A. Aravin, Krista Marran, Shahin Rafii, W. Richard McCombie, Andrew D. Smith, and Gregory J. Hannon. Two waves of De novo methylation during mouse germ cell development. Genes Dev. 28, 1544–1549 (2014).

42. Sergei A. Manakov, Dubravka Pezic, Georgi K. Marinov, William A. Pastor, Ravi Sachidanandam, Alexei A. Aravin MIWI2 and MILI Have Differential Effects on piRNA Biogenesis and DNA Methylation. Cell Rep 12, 1234–1243 (2015)

43. Nishimasu H, Ishizu H, Saito K, Fukuhara S, Kamatani MK, Bonnefond L, Matsumoto N, Nishizawa T, Nakanaga K, Aoki J, Ishitani R, Siomi H, Siomi MC, Nureki O. Structure and function of Zucchini endoribonuclease in piRNA biogenesis. Nature 491, 284–287 (2012).

44. Toru Nishimura, Ippei Nagamori, Tsunetoshi Nakatani, Natsuko Izumi, Yukihide Tomari, Satomi Kuramochi-Miyagawa, Toru Nakano PNLDC1, mouse pre-piRNA Trimmer, is required for meiotic and post-meiotic male germ cell development. EMBO Rep, 19(3):e44957 (2018)

45. Parker JS, Barford D. Argonaute: A scaffold for the function of short regulatory RNAs. Trends Biochem Sci. 31(11):622-30. (2006)

46. Pandey RR, Tokuzawa Y, Yang Z, Hayashi E, Ichisaka T, Kajita S, Asano Y, Kunieda T, Sachidanandam R, Chuma S, Yamanaka S, Pillai RS. Tudor domain containing 12 (TDRD12) is essential for secondary PIWI interacting RNA biogenesis in mice. Proc Natl Acad Sci USA. ;110(41):16492-7. (2013)

47. Pezic, D., Manakov, S. A., Sachidanandam, R. & Aravin, A. A. piRNA pathway targets active LINE1 elements to establish the repressive H3K9me3 mark in germ cells. Genes Dev. 28, 1410–1428 (2014).

48. Reuter M, Berninger P, Chuma S, Shah H, Hosokawa M, Funaya C, Antony C, Sachidanandam R, Pillai RS. Miwi catalysis is required for piRNA amplification-independent LINE1 transposon silencing. Nature. 27;480(7376):264-7. (2011)

49. Skowronski J, Fanning TG, Singer MF. Unit-length line-1 transcripts in human teratocarcinoma cells. Mol Cell Biol. Apr;8(4):1385-97. (1988)

50. Speek M. Antisense promoter of human L1 retrotransposon drives transcription of adjacent cellular genes. Mol Cell Biol. 21(6):1973-1985. (2001)

51. Sakai Y, Suetake I, Shinozaki F, Yamashina S, Tajima S. Co-expression of de novo DNA methyltransferases Dnmt3a2 and Dnmt3L in gonocytes of mouse embryos. Gene Expr Patterns. 2004; 5(2):231–7. (2004)

52. Sophie La Salle, Christopher C Oakes, Oana R Neaga, Déborah Bourc'his, Timothy H Bestor, Jacquetta M Trasler Loss of spermatogonia and wide-spread DNA methylation defects in newborn malemice deficient in DNMT3L. BMC Dev Biol. 2007; 7: 104. (2007)

53. Stefanie Seisenberger, Simon Andrews, Felix Krueger, Julia Arand, Jo¨ rn Walter, Fa´tima Santos, Christian Popp, Bernard Thienpont, Wendy Dean, and Wolf Reik The Dynamics of Genome-wide DNA Methylation Reprogramming in Mouse Primordial Germ Cells. Mol. Cell, 48(6), 849-862, (2012)

54. Suzuki R, Honda S, Kirino Y. PIWI Expression and Function in Cancer. Front Genet. 2012;3:204. (2012)

55. Snead NM, Wu X, Li A, Cui Q, Sakurai K, Burnett JC, Rossi JJ. Molecular basis for improved gene silencing by Dicer substrate interfering RNA compared with other siRNA variants. Nucleic Acids Res. 41(12):6209-21. (2013)

56. Arijita Sarkar, Ranjan Kumar Maji, Sudipto Saha and Zhumur Ghosh piRNAQuest: searching the piRNAome for silencers. BMC Genomics, 15:555 (2014)

57. Shoji K, Katsuma S. Is the expression ofsense and antisense transgenes really sufficient for artificial piRNA production? Curr Biol 25: R708– R710. (2015)

58. Mònica Suelves, Elvira Carrió, Yaiza Núñez-Álvarez, Miguel A. Peinado DNA methylation dynamics in cellular commitment and differentiation. Brief Funct Genomics. 15(6):443-453 (2016)

59. Setten RL, Rossi JJ, Han SP. The current state and future directions of RNAi-based therapeutics. Nat Rev Drug Discov. 2019 Jun;18(6):421-446. (2019)

60. Toshiaki Watanabe, Shin-ichi Tomizawa, Kohzoh Mitsuya, Yasushi Totoki, Yasuhiro Yamamoto, Satomi KuramochiMiyagawa, Naoko Iida, Yuko Hoki, Patrick J. Murphy, Atsushi Toyoda, Kengo Gotoh, Hitoshi Hiura, Takahiro Arima, Asao Fujiyama, Takashi Sado, Tatsuhiro Shibata, Toru Nakano, Haifan Lin, Kenji Ichiyanagi, Paul D. Soloway, and Hiroyuki Sasaki Role for piRNAs and Noncoding RNA in de Novo DNA Methylation of the Imprinted Mouse Rasgrf1 Locus. Science. 332(6031): 848–852. (2011)

61. Marius Walter. Transposon regulation upon dynamic loss of DNA methylation. Development Biology. Université Pierre et Marie Curie - Paris VI (2015)

62. Wenda JM, Homolka D, Yang Z, Spinelli P, Sachidanandam R, Pandey RR, Pillai RS. Distinct Roles of RNA Helicases MVH and TDRD9 in PIWI Slicing-Triggered Mammalian piRNA Biogenesis and Function. Dev Cell. 19;41(6):623-637.e9. (2017)

63. Yamaguchi Y, Ijiri TW, Hata K, Li E, Matsuda Y, Kimura T, Okabe M, Sakaki Y, Sasaki H, Nakano T. DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes. Genes Dev. 22, 908–917 (2008).

64. Zheng K, Wang PJ Blockade of Pachytene piRNA Biogenesis Reveals a Novel Requirement for Maintaining Post-Meiotic Germline Genome Integrity. PLoS Genet 8(11) (2012)

65. Vanessa Zanni, Angéline Eymery,, Michael Coiffet, Matthias Zytnicki, Isabelle Luyten, Hadi Quesneville, Chantal Vaury, and Silke Jensena, Distribution, evolution, and diversity of retrotransposons at the flamenco locus reflect the regulatory properties of piRNA clusters. Proc. Natl. Acad. Sci. USA 110, 19842–19847. (2013)

66. Zhang P, Si X, Skogerbø G, Wang J, Cui D, Li Y, Sun X, Liu L, Sun B, Chen R, He S, Huang DW. piRBase: a web resource assisting piRNA functional study. Database, bau110 (2014)

参考文献をもっと見る

全国の大学の
卒論・修論・学位論文

一発検索!

この論文の関連論文を見る