Long noncoding RNA functionality in imprinted domain regulation

Autoři: William A. MacDonald aff001;  Mellissa R. W. Mann aff003
Působiště autorů: Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America aff001;  Rangos Research Center, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States of America aff002;  Department of Obstetrics, Gynaecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America aff003;  Magee-Womens Research Institute, Pittsburgh, Pennsylvania, United States of America aff004
Vyšlo v časopise: Long noncoding RNA functionality in imprinted domain regulation. PLoS Genet 16(8): e32767. doi:10.1371/journal.pgen.1008930
Kategorie: Review
doi: 10.1371/journal.pgen.1008930


Genomic imprinting is a parent-of-origin dependent phenomenon that restricts transcription to predominantly one parental allele. Since the discovery of the first long noncoding RNA (lncRNA), which notably was an imprinted lncRNA, a body of knowledge has demonstrated pivotal roles for imprinted lncRNAs in regulating parental-specific expression of neighboring imprinted genes. In this Review, we will discuss the multiple functionalities attributed to lncRNAs and how they regulate imprinted gene expression. We also raise unresolved questions about imprinted lncRNA function, which may lead to new avenues of investigation. This Review is dedicated to the memory of Denise Barlow, a giant in the field of genomic imprinting and functional lncRNAs. With her passion for understanding the inner workings of science, her indominable spirit and her consummate curiosity, Denise blazed a path of scientific investigation that made many seminal contributions to genomic imprinting and the wider field of epigenetic regulation, in addition to inspiring future generations of scientists.

Klíčová slova:

DNA transcription – Gene expression – Gene regulation – Genetic interference – Genomic imprinting – Chromatin – Long non-coding RNA – RNA structure


1. Brannan CI, Dees EC, Ingram RS, Tilghman SM. The product of the H19 gene may function as an RNA. Mol Cell Biol. 1990;10: 28–36. doi: 10.1128/mcb.10.1.28 1688465

2. Brown CJ, Ballabio A, Rupert JL, Lafrenière RG, Grompe M, Tonlorenzi R, et al. A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature. 1991;349: 38–44. doi: 10.1038/349038a0 1985261

3. Cabili MN, Trapnell C, Goff L, Koziol M, Tazon-Vega B, Regev A, et al. Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev. Cold Spring Harbor Lab; 2011;25: 1915–1927. doi: 10.1101/gad.17446611 21890647

4. Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H, et al. The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res. 2012;22: 1775–1789. doi: 10.1101/gr.132159.111 22955988

5. ENCODE Project Consortium, Birney E, Stamatoyannopoulos JA, Dutta A, Guigó R, Gingeras TR, et al. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature. 2007;447: 799–816. doi: 10.1038/nature05874 17571346

6. Katayama S, Tomaru Y, Kasukawa T, Waki K, Nakanishi M, Nakamura M, et al. Antisense transcription in the mammalian transcriptome. Science. 2005;309: 1564–1566. doi: 10.1126/science.1112009 16141073

7. Okazaki Y, Furuno M, Kasukawa T, Adachi J, Bono H, Kondo S, et al. Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs. Nature. 2002;420: 563–573. doi: 10.1038/nature01266 12466851

8. Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, et al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 2009;458: 223–227. doi: 10.1038/nature07672 19182780

9. Loda A, Heard E. Xist RNA in action: Past, present, and future. PLoS Genet. 2019;15: e1008333. doi: 10.1371/journal.pgen.1008333 31537017

10. Barlow DP, Bartolomei MS. Genomic imprinting in mammals. Cold Spring Harb Perspect Biol. Cold Spring Harbor Lab; 2014;6: a018382. doi: 10.1101/cshperspect.a018382 24492710

11. Wutz A, Smrzka OW, Schweifer N, Schellander K, Wagner EF, Barlow DP. Imprinted expression of the Igf2r gene depends on an intronic CpG island. Nature. 1997;389: 745–749. doi: 10.1038/39631 9338788

12. Williamson CM, Turner MD, Ball ST, Nottingham WT, Glenister P, Fray M, et al. Identification of an imprinting control region affecting the expression of all transcripts in the Gnas cluster. Nat Genet. 2006;38: 350–355. doi: 10.1038/ng1731 16462745

13. Thorvaldsen JL, Duran KL, Bartolomei MS. Deletion of the H19 differentially methylated domain results in loss of imprinted expression of H19 and Igf2. Genes Dev. 1998;12: 3693–3702. doi: 10.1101/gad.12.23.3693 9851976

14. Lin S-P, Youngson N, Takada S, Seitz H, Reik W, Paulsen M, et al. Asymmetric regulation of imprinting on the maternal and paternal chromosomes at the Dlk1-Gtl2 imprinted cluster on mouse chromosome 12. Nat Genet. 2003;35: 97–102. doi: 10.1038/ng1233 12937418

15. Fitzpatrick GV, Soloway PD, Higgins MJ. Regional loss of imprinting and growth deficiency in mice with a targeted deletion of KvDMR1. Nat Genet. 2002;32: 426–431. doi: 10.1038/ng988 12410230

16. Bielinska B, Blaydes SM, Buiting K, Yang T, Krajewska-Walasek M, Horsthemke B, et al. De novo deletions of SNRPN exon 1 in early human and mouse embryos result in a paternal to maternal imprint switch. Nat Genet. 2000;25: 74–78. doi: 10.1038/75629 10802660

17. Morison IM, Ramsay JP, Spencer HG. A census of mammalian imprinting. Trends in genetics: TIG. 2005;21: 457–465. doi: 10.1016/j.tig.2005.06.008 15990197

18. Williamson CM, Blake A, Thomas S, Beechey CV, Hancock J, Cattanach BM, et al. MRC Harwell, Oxfordshire. World Wide Web Site—Mouse Imprinting Data and References - https://www.mousebook.org/mousebook-catalogs/imprinting-resource (2013).

19. Monk D, Mackay DJG, Eggermann T, Maher ER, Riccio A. Genomic imprinting disorders: lessons on how genome, epigenome and environment interact. Nat Rev Genet. Nature Publishing Group; 2019;20: 235–248. doi: 10.1038/s41576-018-0092-0 30647469

20. Tucci V, Isles AR, Kelsey G, Ferguson-Smith AC, Erice Imprinting Group. Genomic Imprinting and Physiological Processes in Mammals. Cell. 2019;176: 952–965. doi: 10.1016/j.cell.2019.01.043 30794780

21. Guenzl PM, Barlow DP. Macro lncRNAs: a new layer of cis-regulatory information in the mammalian genome. RNA biology. 2012;9: 731–741. doi: 10.4161/rna.19985 22617879

22. Schertzer MD, Braceros KCA, Starmer J, Cherney RE, Lee DM, Salazar G, et al. lncRNA-Induced Spread of Polycomb Controlled by Genome Architecture, RNA Abundance, and CpG Island DNA. Mol Cell. 2019;75: 523–537.e10. doi: 10.1016/j.molcel.2019.05.028 31256989

23. Sachani SS, Landschoot LS, Zhang L, White CR, MacDonald WA, Golding MC, et al. Nucleoporin 107, 62 and 153 mediate Kcnq1ot1 imprinted domain regulation in extraembryonic endoderm stem cells. Nat Commun. 2018;9: 2795. doi: 10.1038/s41467-018-05208-2 30022050

24. Kota SK, Llères D, Bouschet T, Hirasawa R, Marchand A, Begon-Pescia C, et al. ICR Noncoding RNA Expression Controls Imprinting and DNA Replication at the Dlk1-Dio3 Domain. Dev Cell. Elsevier; 2014;31: 19–33. doi: 10.1016/j.devcel.2014.08.009 25263792

25. Seidl CIM, Stricker SH, Barlow DP. The imprinted Air ncRNA is an atypical RNAPII transcript that evades splicing and escapes nuclear export. EMBO J. 2006;25: 3565–3575. doi: 10.1038/sj.emboj.7601245 16874305

26. Clark MB, Johnston RL, Inostroza-Ponta M, Fox AH, Fortini E, Moscato P, et al. Genome-wide analysis of long noncoding RNA stability. Genome Res. 2012;22: 885–898. doi: 10.1101/gr.131037.111 22406755

27. Terranova R, Yokobayashi S, Stadler MB, Otte AP, van Lohuizen M, Orkin SH, et al. Polycomb group proteins Ezh2 and Rnf2 direct genomic contraction and imprinted repression in early mouse embryos. Dev Cell. 2008;15: 668–679. doi: 10.1016/j.devcel.2008.08.015 18848501

28. Tibbit CJ, Williamson CM, Mehta S, Ball ST, Chotalia M, Nottingham WT, et al. Antisense Activity across the Nesp Promoter is Required for Nespas-Mediated Silencing in the Imprinted Gnas Cluster. Noncoding RNA. 2015;1: 246–265. doi: 10.3390/ncrna1030246 29861426

29. White CR, MacDonald WA, Mann MRW. Conservation of DNA Methylation Programming Between Mouse and Human Gametes and Preimplantation Embryos. Biol Reprod. Society for the Study of Reproduction; 2016;: biolreprod.116.140319. doi: 10.1095/biolreprod.116.140319 27465133

30. MacDonald WA, Mann MRW. Epigenetic regulation of genomic imprinting from germ line to preimplantation. 2014;81: 126–140. doi: 10.1002/mrd.22220 23893518

31. Stewart KR, Veselovska L, Kelsey G. Establishment and functions of DNA methylation in the germline. Epigenomics. 2016;8: 1399–1413. doi: 10.2217/epi-2016-0056 27659720

32. Pauler FM, Barlow DP, Hudson QJ. Mechanisms of long range silencing by imprinted macro non-coding RNAs. Curr Opin Genet Dev. 2012;22: 283–289. doi: 10.1016/j.gde.2012.02.005 22386265

33. Furuno M, Pang KC, Ninomiya N, Fukuda S, Frith MC, Bult C, et al. Clusters of internally primed transcripts reveal novel long noncoding RNAs. PLoS Genet. 2006;2: e37. doi: 10.1371/journal.pgen.0020037 16683026

34. Pauler FM, Koerner MV, Barlow DP. Silencing by imprinted noncoding RNAs: is transcription the answer? Trends in genetics: TIG. 2007;23: 284–292. doi: 10.1016/j.tig.2007.03.018 17445943

35. Hao N, Palmer AC, Dodd IB, Shearwin KE. Directing traffic on DNA-How transcription factors relieve or induce transcriptional interference. Transcription. 2017;8: 120–125. doi: 10.1080/21541264.2017.1285851 28129043

36. Latos PA, Pauler FM, Koerner MV, Şenergin HB, Hudson QJ, Stocsits RR, et al. Airn transcriptional overlap, but not its lncRNA products, induces imprinted Igf2r silencing. Science. 2012;338: 1469–1472. doi: 10.1126/science.1228110 23239737

37. Huang R, Jaritz M, Guenzl P, Vlatkovic I, Sommer A, Tamir IM, et al. An RNA-Seq strategy to detect the complete coding and non-coding transcriptome including full-length imprinted macro ncRNAs. Huang R, Jaritz M, Guenzl P, Vlatkovic I, Sommer A, Tamir IM, et al., editors. PLoS ONE. 2011;6: e27288. doi: 10.1371/journal.pone.0027288 22102886

38. Latos PA, Barlow DP. Regulation of imprinted expression by macro non-coding RNAs. RNA biology. 2009;6: 100–106. doi: 10.4161/rna.6.2.7854 19229135

39. Sleutels F, Zwart R, Barlow DP. The non-coding Air RNA is required for silencing autosomal imprinted genes. Nature. 2002;415: 810–813. doi: 10.1038/415810a 11845212

40. Santoro F, Mayer D, Klement RM, Warczok KE, Stukalov A, Barlow DP, et al. Imprinted Igf2r silencing depends on continuous Airn lncRNA expression and is not restricted to a developmental window. Development. The Company of Biologists Limited; 2013;140: 1184–1195. doi: 10.1242/dev.088849 23444351

41. Andergassen D, Muckenhuber M, Bammer PC, Kulinski TM, Theussl H-C, Shimizu T, et al. The Airn lncRNA does not require any DNA elements within its locus to silence distant imprinted genes. Bartolomei MS, editor. PLoS Genet. 2019;15: e1008268. doi: 10.1371/journal.pgen.1008268 31329595

42. Meng L, Person RE, Huang W, Zhu PJ, Costa-Mattioli M, Beaudet AL. Truncation of Ube3a-ATS unsilences paternal Ube3a and ameliorates behavioral defects in the Angelman syndrome mouse model. Bartolomei MS, editor. PLoS Genet. 2013;9: e1004039. doi: 10.1371/journal.pgen.1004039 24385930

43. Landers M, Bancescu DL, Le Meur E, Rougeulle C, Glatt-Deeley H, Brannan C, et al. Regulation of the large (approximately 1000 kb) imprinted murine Ube3a antisense transcript by alternative exons upstream of Snurf/Snrpn. Nucleic Acids Res. Oxford University Press; 2004;32: 3480–3492. doi: 10.1093/nar/gkh670 15226413

44. Lewis MW, Vargas-Franco D, Morse DA, Resnick JL. A mouse model of Angelman syndrome imprinting defects. Hum Mol Genet. 2019;28: 220–229. doi: 10.1093/hmg/ddy345 30260400

45. Bressler J, Tsai TF, Wu MY, Tsai SF, Ramirez MA, Armstrong D, et al. The SNRPN promoter is not required for genomic imprinting of the Prader-Willi/Angelman domain in mice. Nat Genet. 2001;28: 232–240. doi: 10.1038/90067 11431693

46. Meng L, Person RE, Beaudet AL. Ube3a-ATS is an atypical RNA polymerase II transcript that represses the paternal expression of Ube3a. Hum Mol Genet. Oxford University Press; 2012;21: 3001–3012. doi: 10.1093/hmg/dds130 22493002

47. Powell WT, Coulson RL, Gonzales ML, Crary FK, Wong SS, Adams S, et al. R-loop formation at Snord116 mediates topotecan inhibition of Ube3a-antisense and allele-specific chromatin decondensation. Proceedings of the National Academy of Sciences. National Acad Sciences; 2013;110: 13938–13943. doi: 10.1073/pnas.1305426110 23918391

48. Mancini-Dinardo D, Steele SJS, Levorse JM, Ingram RS, Tilghman SM. Elongation of the Kcnq1ot1 transcript is required for genomic imprinting of neighboring genes. Genes Dev. Cold Spring Harbor Lab; 2006;20: 1268–1282. doi: 10.1101/gad.1416906 16702402

49. Shin J-Y, Fitzpatrick GV, Higgins MJ. Two distinct mechanisms of silencing by the KvDMR1 imprinting control region. EMBO J. 2008;27: 168–178. doi: 10.1038/sj.emboj.7601960 18079696

50. Golding MC, Magri LS, Zhang L, Lalone SA, Higgins MJ, Mann MRW. Depletion of Kcnq1ot1 non-coding RNA does not affect imprinting maintenance in stem cells. Development. 2011;138: 3667–3678. doi: 10.1242/dev.057778 21775415

51. Redrup L, Branco MR, Perdeaux ER, Krueger C, Lewis A, Santos F, et al. The long noncoding RNA Kcnq1ot1 organises a lineage-specific nuclear domain for epigenetic gene silencing. Development. 2009;136: 525–530. doi: 10.1242/dev.031328 19144718

52. Pandey RR, Mondal T, Mohammad F, Enroth S, Redrup L, Komorowski J, et al. Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. Mol Cell. 2008;32: 232–246. doi: 10.1016/j.molcel.2008.08.022 18951091

53. Yatsuki H, Joh K, Higashimoto K, Soejima H, Arai Y, Wang Y, et al. Domain regulation of imprinting cluster in Kip2/Lit1 subdomain on mouse chromosome 7F4/F5: large-scale DNA methylation analysis reveals that DMR-Lit1 is a putative imprinting control region. Genome Research. 2002;12: 1860–1870. doi: 10.1101/gr.110702 12466290

54. Williamson CM, Ball ST, Dawson C, Mehta S, Beechey CV, Fray M, et al. Uncoupling antisense-mediated silencing and DNA methylation in the imprinted Gnas cluster. PLoS Genet. 2011;7: e1001347. doi: 10.1371/journal.pgen.1001347 21455290

55. Mehta S, Williamson CM, Ball S, Tibbit C, Beechey C, Fray M, et al. Transcription driven somatic DNA methylation within the imprinted Gnas cluster. El-Maarri O, editor. PLoS ONE. Public Library of Science; 2015;10: e0117378. doi: 10.1371/journal.pone.0117378 25659103

56. Royo H, Bortolin M-L, Seitz H, Cavaille J. Small non-coding RNAs and genomic imprinting. Cytogenet Genome Res. Karger Publishers; 2006;113: 99–108. doi: 10.1159/000090820 16575168

57. Lehnert S, Kapitonov V, Thilakarathne PJ, Schuit FC. Modeling the asymmetric evolution of a mouse and rat-specific microRNA gene cluster intron 10 of the Sfmbt2 gene. BMC Genomics. BioMed Central; 2011;12: 257–11. doi: 10.1186/1471-2164-12-257 21605348

58. Inoue K, Hirose M, Inoue H, Hatanaka Y, Honda A, Hasegawa A, et al. The Rodent-Specific MicroRNA Cluster within the Sfmbt2 Gene Is Imprinted and Essential for Placental Development. CellReports. 2017;19: 949–956. doi: 10.1016/j.celrep.2017.04.018 28467908

59. Watanabe T, Totoki Y, Toyoda A, Kaneda M, Kuramochi-Miyagawa S, Obata Y, et al. Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes. Nature. 2008;453: 539–543. doi: 10.1038/nature06908 18404146

60. Cavaille J, Buiting K, Kiefmann M, Lalande M, Brannan CI, Horsthemke B, et al. Identification of brain-specific and imprinted small nucleolar RNA genes exhibiting an unusual genomic organization. Proc Natl Acad Sci USA. National Academy of Sciences; 2000;97: 14311–14316. doi: 10.1073/pnas.250426397 11106375

61. Cai X, Cullen BR. The imprinted H19 noncoding RNA is a primary microRNA precursor. RNA. Cold Spring Harbor Lab; 2007;13: 313–316. doi: 10.1261/rna.351707 17237358

62. Robson JE, Eaton SA, Underhill P, Williams D, Peters J. MicroRNAs 296 and 298 are imprinted and part of the GNAS/Gnas cluster and miR-296 targets IKBKE and Tmed9. RNA. 2012;18: 135–144. doi: 10.1261/rna.029561.111 22114321

63. Seitz H, Royo H, Bortolin M-L, Lin S-P, Ferguson-Smith AC, Cavaillé J. A large imprinted microRNA gene cluster at the mouse Dlk1-Gtl2 domain. Genome Research. 2004;14: 1741–1748. doi: 10.1101/gr.2743304 15310658

64. Labialle S, Marty V, Bortolin-Cavaillé M-L, Hoareau-Osman M, Pradère J-P, Valet P, et al. The miR-379/miR-410 cluster at the imprinted Dlk1-Dio3 domain controls neonatal metabolic adaptation. EMBO J. 2014;33: 2216–2230. doi: 10.15252/embj.201387038 25124681

65. Gao Y-Q, Chen X, Wang P, Lu L, Zhao W, Chen C, et al. Regulation of DLK1 by the maternally expressed miR-379/miR-544 cluster may underlie callipyge polar overdominance inheritance. Proceedings of the National Academy of Sciences. 2015;112: 13627–13632. doi: 10.1073/pnas.1511448112 26487685

66. Kircher M, Bock C, Paulsen M. Structural conservation versus functional divergence of maternally expressed microRNAs in the Dlk1/Gtl2 imprinting region. BMC Genomics. 2008;9: 346. doi: 10.1186/1471-2164-9-346 18651963

67. Bortolin-Cavaillé M-L, Dance M, Weber M, Cavaillé J. C19MC microRNAs are processed from introns of large Pol-II, non-protein-coding transcripts. Nucleic Acids Res. Oxford University Press; 2009;37: 3464–3473. doi: 10.1093/nar/gkp205 19339516

68. Girardot M, Cavaillé J, Feil R. Small regulatory RNAs controlled by genomic imprinting and their contribution to human disease. Epigenetics. 2012;7: 1341–1348. doi: 10.4161/epi.22884 23154539

69. Kumamoto S, Takahashi N, Nomura K, Fujiwara M, Kijioka M, Uno Y, et al. Overexpression of microRNAs from the Gtl2-Rian locus contributes to postnatal death in mice. Hum Mol Genet. 2017;26: 3653–3662. doi: 10.1093/hmg/ddx223 28934383

70. Ito M, Sferruzzi-Perri AN, Edwards CA, Adalsteinsson BT, Allen SE, Loo T-H, et al. A trans-homologue interaction between reciprocally imprinted miR-127 and Rtl1 regulates placenta development. Development. Oxford University Press for The Company of Biologists Limited; 2015;142: 2425–2430. doi: 10.1242/dev.121996 26138477

71. Davis E, Caiment F, Tordoir X, Cavaillé J, Ferguson-Smith A, Cockett N, et al. RNAi-mediated allelic trans-interaction at the imprinted Rtl1/Peg11 locus. Curr Biol. 2005;15: 743–749. doi: 10.1016/j.cub.2005.02.060 15854907

72. Hagan JP, O'Neill BL, Stewart CL, Kozlov SV, Croce CM. At least ten genes define the imprinted Dlk1-Dio3 cluster on mouse chromosome 12qF1. Aramayo R, editor. PLoS ONE. Public Library of Science; 2009;4: e4352. doi: 10.1371/journal.pone.0004352 19194500

73. Tsai M-C, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, et al. Long noncoding RNA as modular scaffold of histone modification complexes. Science. 2010;329: 689–693. doi: 10.1126/science.1192002 20616235

74. Koerner MV, Pauler FM, Huang R, Barlow DP. The function of non-coding RNAs in genomic imprinting. Development. The Company of Biologists Limited; 2009;136: 1771–1783. doi: 10.1242/dev.030403 19429783

75. Wang KC, Chang HY. Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011;43: 904–914. doi: 10.1016/j.molcel.2011.08.018 21925379

76. Yang Y, Wen L, Zhu H. Unveiling the hidden function of long non-coding RNA by identifying its major partner-protein. Cell Biosci. BioMed Central; 2015;5: 59–10. doi: 10.1186/s13578-015-0050-x 26500759

77. Nagano T, Mitchell JA, Sanz LA, Pauler FM, Ferguson-Smith AC, Feil R, et al. The Air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin. Science. 2008;322: 1717–1720. doi: 10.1126/science.1163802 18988810

78. Zhao J, Ohsumi TK, Kung JT, Ogawa Y, Grau DJ, Sarma K, et al. Genome-wide identification of polycomb-associated RNAs by RIP-seq. Mol Cell. 2010;40: 939–953. doi: 10.1016/j.molcel.2010.12.011 21172659

79. Mohammad F, Pandey GK, Mondal T, Enroth S, Redrup L, Gyllensten U, et al. Long noncoding RNA-mediated maintenance of DNA methylation and transcriptional gene silencing. Development. 2012;139: 2792–2803. doi: 10.1242/dev.079566 22721776

80. Mohammad F, Pandey RR, Nagano T, Chakalova L, Mondal T, Fraser P, et al. Kcnq1ot1/Lit1 noncoding RNA mediates transcriptional silencing by targeting to the perinucleolar region. Mol Cell Biol. American Society for Microbiology; 2008;28: 3713–3728. doi: 10.1128/MCB.02263-07 18299392

81. Fedoriw AM, Calabrese JM, Mu W, Yee D, Magnuson T. Differentiation-driven nucleolar association of the mouse imprinted Kcnq1 locus. G3 (Bethesda). Genetics Society of America; 2012;2: 1521–1528. doi: 10.1534/g3.112.004226 23275875

82. Lewis A, Green K, Dawson C, Redrup L, Huynh KD, Lee JT, et al. Epigenetic dynamics of the Kcnq1 imprinted domain in the early embryo. Development. 2006;133: 4203–4210. doi: 10.1242/dev.02612 17021040

83. Lewis A, Mitsuya K, Umlauf D, Smith P, Dean W, Walter J, et al. Imprinting on distal chromosome 7 in the placenta involves repressive histone methylation independent of DNA methylation. Nat Genet. 2004;36: 1291–1295. doi: 10.1038/ng1468 15516931

84. Umlauf D, Goto Y, Cao R, Cerqueira F, Wagschal A, Zhang Y, et al. Imprinting along the Kcnq1 domain on mouse chromosome 7 involves repressive histone methylation and recruitment of Polycomb group complexes. Nat Genet. 2004;36: 1296–1300. doi: 10.1038/ng1467 15516932

85. Mohammad F, Mondal T, Guseva N, Pandey GK, Kanduri C. Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1. Development. 2010;137: 2493–2499. doi: 10.1242/dev.048181 20573698

86. Wagschal A, Sutherland HG, Woodfine K, Henckel A, Chebli K, Schulz R, et al. G9a histone methyltransferase contributes to imprinting in the mouse placenta. Mol Cell Biol. 2008;28: 1104–1113. doi: 10.1128/MCB.01111-07 18039842

87. Sanli I, Lalevée S, Cammisa M, Perrin A, Rage F, Llères D, et al. Meg3 Non-coding RNA Expression Controls Imprinting by Preventing Transcriptional Upregulation in cis. CellReports. 2018;23: 337–348. doi: 10.1016/j.celrep.2018.03.044 29641995

88. Kaneko S, Bonasio R, Saldaña-Meyer R, Yoshida T, Son J, Nishino K, et al. Interactions between JARID2 and noncoding RNAs regulate PRC2 recruitment to chromatin. Mol Cell. 2014;53: 290–300. doi: 10.1016/j.molcel.2013.11.012 24374312

89. Davidovich C, Cech TR. The recruitment of chromatin modifiers by long noncoding RNAs: lessons from PRC2. RNA. 2015;21: 2007–2022. doi: 10.1261/rna.053918.115 26574518

90. He S, Zhang H, Liu H, Zhu H. LongTarget: a tool to predict lncRNA DNA-binding motifs and binding sites via Hoogsteen base-pairing analysis. Bioinformatics. 2015;31: 178–186. doi: 10.1093/bioinformatics/btu643 25262155

91. Sherpa C, Rausch JW, Le Grice SF. Structural characterization of maternally expressed gene 3 RNA reveals conserved motifs and potential sites of interaction with polycomb repressive complex 2. Nucleic Acids Res. 2018;46: 10432–10447. doi: 10.1093/nar/gky722 30102382

92. Kanhere A, Jenner RG. Noncoding RNA localisation mechanisms in chromatin regulation. Silence. 2012;3: 2. doi: 10.1186/1758-907X-3-2 22292981

93. Cifuentes-Rojas C, Hernandez AJ, Sarma K, Lee JT. Regulatory interactions between RNA and polycomb repressive complex 2. Mol Cell. 2014;55: 171–185. doi: 10.1016/j.molcel.2014.05.009 24882207

94. Kaneko S, Li G, Son J, Xu C-F, Margueron R, Neubert TA, et al. Phosphorylation of the PRC2 component Ezh2 is cell cycle-regulated and up-regulates its binding to ncRNA. Genes Dev. Cold Spring Harbor Lab; 2010;24: 2615–2620. doi: 10.1101/gad.1983810 21123648

95. Zhao J, Sun BK, Erwin JA, Song JJ, Lee JT. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science. American Association for the Advancement of Science; 2008;322: 750–756. doi: 10.1126/science.1163045 18974356

96. Wang X, Goodrich KJ, Gooding AR, Naeem H, Archer S, Paucek RD, et al. Targeting of Polycomb Repressive Complex 2 to RNA by Short Repeats of Consecutive Guanines. Mol Cell. 2017;65: 1056–1067.e5. doi: 10.1016/j.molcel.2017.02.003 28306504

97. Das PP, Hendrix DA, Apostolou E, Buchner AH, Canver MC, Beyaz S, et al. PRC2 Is Required to Maintain Expression of the Maternal Gtl2-Rian-Mirg Locus by Preventing De Novo DNA Methylation in Mouse Embryonic Stem Cells. CellReports. 2015;12: 1456–1470. doi: 10.1016/j.celrep.2015.07.053 26299972

98. Luo Z, Lin C, Woodfin AR, Bartom ET, Gao X, Smith ER, et al. Regulation of the imprinted Dlk1-Dio3 locus by allele-specific enhancer activity. Genes Dev. Cold Spring Harbor Lab; 2016;30: 92–101. doi: 10.1101/gad.270413.115 26728555

99. Yen Y-P, Hsieh W-F, Tsai Y-Y, Lu Y-L, Liau ES, Hsu H-C, et al. Dlk1-Dio3 locus-derived lncRNAs perpetuate postmitotic motor neuron cell fate and subtype identity. Elife. 2018;7: 178. doi: 10.7554/eLife.38080 30311912

100. Kornienko AE, Guenzl PM, Barlow DP, Pauler FM. Gene regulation by the act of long non-coding RNA transcription. BMC biology. BioMed Central; 2013;11: 59. doi: 10.1186/1741-7007-11-59 23721193

101. Gabory A, Ripoche M-A, Le Digarcher A, Watrin F, Ziyyat A, Forné T, et al. H19 acts as a trans regulator of the imprinted gene network controlling growth in mice. Development. 2009;136: 3413–3421. doi: 10.1242/dev.036061 19762426

102. Stelzer Y, Sagi I, Yanuka O, Eiges R, Benvenisty N. The noncoding RNA IPW regulates the imprinted DLK1-DIO3 locus in an induced pluripotent stem cell model of Prader-Willi syndrome. Nat Genet. 2014;46: 551–557. doi: 10.1038/ng.2968 24816254

103. Lahbib-Mansais Y, Barasc H, Marti-Marimon M, Mompart F, Iannuccelli E, Robelin D, et al. Expressed alleles of imprinted IGF2, DLK1 and MEG3 colocalize in 3D-preserved nuclei of porcine fetal cells. BMC Cell Biol. 2016;17: 35. doi: 10.1186/s12860-016-0113-9 27716032

104. Marti-Marimon M, Vialaneix N, Voillet V, Yerle-Bouissou M, Lahbib-Mansais Y, Liaubet L. A new approach of gene co-expression network inference reveals significant biological processes involved in porcine muscle development in late gestation. Sci Rep. Nature Publishing Group; 2018;8: 10150–13. doi: 10.1038/s41598-018-28173-8 29977047

105. Varrault A, Gueydan C, Delalbre A, Bellmann A, Houssami S, Aknin C, et al. Zac1 regulates an imprinted gene network critically involved in the control of embryonic growth. Dev Cell. 2006;11: 711–722. doi: 10.1016/j.devcel.2006.09.003 17084362

106. Wang X, Cheng Z, Dai L, Jiang T, Jia L, Jing X, et al. Knockdown of Long Noncoding RNA H19 Represses the Progress of Pulmonary Fibrosis through the Transforming Growth Factor β/Smad3 Pathway by Regulating MicroRNA 140. Mol Cell Biol. American Society for Microbiology Journals; 2019;39: 431. doi: 10.1128/MCB.00143-19 30988156

107. Mondal T, Subhash S, Vaid R, Enroth S, Uday S, Reinius B, et al. MEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA-DNA triplex structures. Nat Commun. Nature Publishing Group; 2015;6: 7743. doi: 10.1038/ncomms8743 26205790

108. Liang W-C, Fu W-M, Wang Y-B, Sun Y-X, Xu L-L, Wong C-W, et al. H19 activates Wnt signaling and promotes osteoblast differentiation by functioning as a competing endogenous RNA. Sci Rep. Nature Publishing Group; 2016;6: 20121–11. doi: 10.1038/srep20121 26853553

109. Gao Y, Lu X. Decreased expression of MEG3 contributes to retinoblastoma progression and affects retinoblastoma cell growth by regulating the activity of Wnt/β-catenin pathway. Tumour Biol. 2016;37: 1461–1469. doi: 10.1007/s13277-015-4564-y 26662307

110. Yang F, Bi J, Xue X, Zheng L, Zhi K, Hua J, et al. Up-regulated long non-coding RNA H19 contributes to proliferation of gastric cancer cells. FEBS J. 2012;279: 3159–3165. doi: 10.1111/j.1742-4658.2012.08694.x 22776265

111. Zhou Y, Zhong Y, Wang Y, Zhang X, Batista DL, Gejman R, et al. Activation of p53 by MEG3 non-coding RNA. J Biol Chem. American Society for Biochemistry and Molecular Biology; 2007;282: 24731–24742. doi: 10.1074/jbc.M702029200 17569660

112. Monnier P, Martinet C, Pontis J, Stancheva I, Ait-Si-Ali S, Dandolo L. H19 lncRNA controls gene expression of the Imprinted Gene Network by recruiting MBD1. Proceedings of the National Academy of Sciences. 2013;110: 20693–20698. doi: 10.1073/pnas.1310201110 24297921

113. Liu H, Shang X, Zhu H. LncRNA/DNA binding analysis reveals losses and gains and lineage specificity of genomic imprinting in mammals. Bioinformatics. 2017;33: 1431–1436. doi: 10.1093/bioinformatics/btw818 28052924

114. Iyer S, Modali SD, Agarwal SK. Long Noncoding RNA MEG3 Is an Epigenetic Determinant of Oncogenic Signaling in Functional Pancreatic Neuroendocrine Tumor Cells. Mol Cell Biol. 2017;37. doi: 10.1128/MCB.00278-17 28847847

115. Fabbri M, Girnita L, Varani G, Calin GA. Decrypting noncoding RNA interactions, structures, and functional networks. Genome Res. 2019;29: 1377–1388. doi: 10.1101/gr.247239.118 31434680

116. Uroda T, Anastasakou E, Rossi A, Teulon J-M, Pellequer J-L, Annibale P, et al. Conserved Pseudoknots in lncRNA MEG3 Are Essential for Stimulation of the p53 Pathway. Mol Cell. 2019;75: 982–995.e9. doi: 10.1016/j.molcel.2019.07.025 31444106

117. Kurukuti S, Tiwari VK, Tavoosidana G, Pugacheva E, Murrell A, Zhao Z, et al. CTCF binding at the H19 imprinting control region mediates maternally inherited higher-order chromatin conformation to restrict enhancer access to Igf2. Proc Natl Acad Sci USA. 2006;103: 10684–10689. doi: 10.1073/pnas.0600326103 16815976

118. Murrell A, Heeson S, Reik W. Interaction between differentially methylated regions partitions the imprinted genes Igf2 and H19 into parent-specific chromatin loops. Nat Genet. 2004;36: 889–893. doi: 10.1038/ng1402 15273689

119. Szabo P, Tang SH, Rentsendorj A, Pfeifer GP, Mann JR. Maternal-specific footprints at putative CTCF sites in the H19 imprinting control region give evidence for insulator function. Current Biology. 2000;10: 607–610. doi: 10.1016/s0960-9822(00)00489-9 10837224

120. Llères D, Moindrot B, Pathak R, Piras V, Matelot M, Pignard B, et al. CTCF modulates allele-specific sub-TAD organization and imprinted gene activity at the mouse Dlk1-Dio3 and Igf2-H19 domains. Genome Biol. 2019;20: 272. doi: 10.1186/s13059-019-1896-8 31831055

121. Hansen AS, Hsieh T-HS, Cattoglio C, Pustova I, Saldaña-Meyer R, Reinberg D, et al. Distinct Classes of Chromatin Loops Revealed by Deletion of an RNA-Binding Region in CTCF. Mol Cell. 2019;76: 395–411.e13. doi: 10.1016/j.molcel.2019.07.039 31522987

122. Saldaña-Meyer R, Rodriguez-Hernaez J, Escobar T, Nishana M, Jácome-López K, Nora EP, et al. RNA Interactions Are Essential for CTCF-Mediated Genome Organization. Mol Cell. 2019;76: 412–422.e5. doi: 10.1016/j.molcel.2019.08.015 31522988

123. Zhang H, Zeitz MJ, Wang H, Niu B, Ge S, Li W, et al. Long noncoding RNA-mediated intrachromosomal interactions promote imprinting at the Kcnq1 locus. J Cell Biol. 2014;204: 61–75. doi: 10.1083/jcb.201304152 24395636

124. Korostowski L, Sedlak N, Engel N. The Kcnq1ot1 long non-coding RNA affects chromatin conformation and expression of Kcnq1, but does not regulate its imprinting in the developing heart. PLoS Genet. 2012;8: e1002956. doi: 10.1371/journal.pgen.1002956 23028363

125. Long Y, Wang X, Youmans DT, Cech TR. How do lncRNAs regulate transcription? Sci Adv. 2017;3: eaao2110. doi: 10.1126/sciadv.aao2110 28959731

126. Kopp F, Mendell JT. Functional Classification and Experimental Dissection of Long Noncoding RNAs. Cell. 2018;172: 393–407. doi: 10.1016/j.cell.2018.01.011 29373828

Článek vyšel v časopise

PLOS Genetics

2020 Číslo 8
Nejčtenější tento týden
Nejčtenější v tomto čísle
Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.


Nemáte účet?  Registrujte se