A Downstream CpG Island Controls Transcript Initiation and Elongation and the Methylation State of the Imprinted Macro ncRNA Promoter

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A CpG island (CGI) lies at the 5′ end of the Airn macro non-protein-coding (nc) RNA that represses the flanking Igf2r promoter in cis on paternally inherited chromosomes. In addition to being modified on maternally inherited chromosomes by a DNA methylation imprint, the Airn CGI shows two unusual organization features: its position immediately downstream of the Airn promoter and transcription start site and a series of tandem direct repeats (TDRs) occupying its second half. The physical separation of the Airn promoter from the CGI provides a model to investigate if the CGI plays distinct transcriptional and epigenetic roles. We used homologous recombination to generate embryonic stem cells carrying deletions at the endogenous locus of the entire CGI or just the TDRs. The deleted Airn alleles were analyzed by using an ES cell imprinting model that recapitulates the onset of Igf2r imprinted expression in embryonic development or by using knock-out mice. The results show that the CGI is required for efficient Airn initiation and to maintain the unmethylated state of the Airn promoter, which are both necessary for Igf2r repression on the paternal chromosome. The TDRs occupying the second half of the CGI play a minor role in Airn transcriptional elongation or processivity, but are essential for methylation on the maternal Airn promoter that is necessary for Igf2r to be expressed from this chromosome. Together the data indicate the existence of a class of regulatory CGIs in the mammalian genome that act downstream of the promoter and transcription start.

Vyšlo v časopise: A Downstream CpG Island Controls Transcript Initiation and Elongation and the Methylation State of the Imprinted Macro ncRNA Promoter. PLoS Genet 8(3): e32767. doi:10.1371/journal.pgen.1002540
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002540

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1. DeatonAMBirdA 2011 CpG islands and the regulation of transcription. Genes & development 25 1010 1022

2. IllingworthRSGruenewald-SchneiderUWebbSKerrARJamesKD 2010 Orphan CpG islands identify numerous conserved promoters in the mammalian genome. PLoS Genet 6 e1001134 doi:10.1371/journal.pgen.1001134

3. SpahnLBarlowDP 2003 An ICE pattern crystallizes. Nat Genet 35 11 12

4. WanLBBartolomeiMS 2008 Regulation of imprinting in clusters: noncoding RNAs versus insulators. Adv Genet 61 207 223

5. ThorvaldsenJLBartolomeiMS 2007 SnapShot: imprinted gene clusters. Cell 130 958

6. Ferguson-SmithAC 2011 Genomic imprinting: the emergence of an epigenetic paradigm. Nature reviews Genetics 12 565 575

7. AntequeraF 2003 Structure, function and evolution of CpG island promoters. Cell Mol Life Sci 60 1647 1658

8. KobayashiHSudaCAbeTKoharaYIkemuraT 2006 Bisulfite sequencing and dinucleotide content analysis of 15 imprinted mouse differentially methylated regions (DMRs): paternally methylated DMRs contain less CpGs than maternally methylated DMRs. Cytogenet Genome Res 113 130 137

9. TomizawaSKobayashiHWatanabeTAndrewsSHataK 2011 Dynamic stage-specific changes in imprinted differentially methylated regions during early mammalian development and prevalence of non-CpG methylation in oocytes. Development 138 811 820

10. WutzASmrzkaOWSchweiferNSchellanderKWagnerEF 1997 Imprinted expression of the Igf2r gene depends on an intronic CpG island. Nature 389 745 749

11. WilliamsonCMTurnerMDBallSTNottinghamWTGlenisterP 2006 Identification of an imprinting control region affecting the expression of all transcripts in the Gnas cluster. Nat Genet 38 350 355

12. ThorvaldsenJLDuranKLBartolomeiMS 1998 Deletion of the H19 differentially methylated domain results in loss of imprinted expression of H19 and Igf2. Genes Dev 12 3693 3702

13. LinSPYoungsonNTakadaSSeitzHReikW 2003 Asymmetric regulation of imprinting on the maternal and paternal chromosomes at the Dlk1-Gtl2 imprinted cluster on mouse chromosome 12. Nat Genet 35 97 102

14. FitzpatrickGVSolowayPDHigginsMJ 2002 Regional loss of imprinting and growth deficiency in mice with a targeted deletion of KvDMR1. Nat Genet 9 9

15. BielinskaBBlaydesSMBuitingKYangTKrajewska-WalasekM 2000 De novo deletions of SNRPN exon 1 in early human and mouse embryos result in a paternal to maternal imprint switch. Nat Genet 25 74 78

16. KoernerMVPaulerFMHuangRBarlowDP 2009 The function of non-coding RNAs in genomic imprinting. Development 136 1771 1783

17. SantoroFBarlowDP 2011 Developmental control of imprinted expression by macro non-coding RNAs. Seminars in cell & developmental biology

18. Mancini-DinardoDSteeleSJLevorseJMIngramRSTilghmanSM 2006 Elongation of the Kcnq1ot1 transcript is required for genomic imprinting of neighboring genes. Genes Dev 20 1268 1282

19. SleutelsFZwartRBarlowDP 2002 The non-coding Air RNA is required for silencing autosomal imprinted genes. Nature 415 810 813

20. WilliamsonCMBallSTDawsonCMehtaSBeecheyCV 2011 Uncoupling antisense-mediated silencing and DNA methylation in the imprinted Gnas cluster. PLoS Genet 7 e1001347 doi:10.1371/journal.pgen.1001347

21. SeidlCIStrickerSHBarlowDP 2006 The imprinted Air ncRNA is an atypical RNAPII transcript that evades splicing and escapes nuclear export. Embo J 25 3565 3575

22. LiEBeardCJaenischR 1993 Role for DNA methylation in genomic imprinting. Nature 366 362 365

23. OoiSKO'DonnellAHBestorTH 2009 Mammalian cytosine methylation at a glance. J Cell Sci 122 2787 2791

24. LiYSasakiH 2011 Genomic imprinting in mammals: its life cycle, molecular mechanisms and reprogramming. Cell Res

25. ChotaliaMSmallwoodSARufNDawsonCLuciferoD 2009 Transcription is required for establishment of germline methylation marks at imprinted genes. Genes Dev 23 105 117

26. SmallwoodSATomizawaSIKruegerFRufNCarliN 2011 Dynamic CpG island methylation landscape in oocytes and preimplantation embryos. Nature genetics

27. NeumannBKubickaPBarlowDP 1995 Characteristics of imprinted genes. Nat Genet 9 12 13

28. WalterJHutterBKhareTPaulsenM 2006 Repetitive elements in imprinted genes. Cytogenet Genome Res 113 109 115

29. HudsonQJSeidlCIKulinskiTMHuangRWarczokKE 2011 Extra-embryonic-specific imprinted expression is restricted to defined lineages in the post-implantation embryo. Developmental biology 353 420 431

30. PandeyRRMondalTMohammadFEnrothSRedrupL 2008 Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. Mol Cell 32 232 246

31. LatosPAStrickerSHSteenpassLPaulerFMHuangR 2009 An in vitro ES cell imprinting model shows that imprinted expression of the Igf2r gene arises from an allele-specific expression bias. Development 136 437 448

32. StrickerSHSteenpassLPaulerFMSantoroFLatosPA 2008 Silencing and transcriptional properties of the imprinted Airn ncRNA are independent of the endogenous promoter. EMBO J 27 3116 3128

33. RassoulzadeganMMaglianoMCuzinF 2002 Transvection effects involving DNA methylation during meiosis in the mouse. EMBO J 21 440 450

34. TallquistMDSorianoP 2000 Epiblast-restricted Cre expression in MORE mice: a tool to distinguish embryonic vs. extra-embryonic gene function. Genesis 26 113 115

35. BarlowDPStogerRHerrmannBGSaitoKSchweiferN 1991 The mouse insulin-like growth factor type-2 receptor is imprinted and closely linked to the Tme locus. Nature 349 84 87

36. WutzATheusslHCDausmanJJaenischRBarlowDP 2001 Non-imprinted Igf2r expression decreases growth and rescues the Tme mutation in mice. Development 128 1881 1887

37. WangZQFungMRBarlowDPWagnerEF 1994 Regulation of embryonic growth and lysosomal targeting by the imprinted Igf2/Mpr gene. Nature 372 464 467

38. ForejtJGregorovaS 1992 Genetic analysis of genomic imprinting: an Imprintor-1 gene controls inactivation of the paternal copy of the mouse Tme locus. Cell 70 443 450

39. IllingworthRSBirdAP 2009 CpG islands–‘a rough guide’. FEBS Lett 583 1713 1720

40. PaulerFMKoernerMVBarlowDP 2007 Silencing by imprinted noncoding RNAs: is transcription the answer? Trends Genet 23 284 292

41. NaganoTMitchellJASanzLAPaulerFMFerguson-SmithAC 2008 The Air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin. Science 322 1717 1720

42. MagerJMontgomeryNDde VillenaFPMagnusonT 2003 Genome imprinting regulated by the mouse Polycomb group protein Eed. Nat Genet 33 502 507

43. LeeJT 2003 Molecular links between X-inactivation and autosomal imprinting: X-inactivation as a driving force for the evolution of imprinting? Curr Biol 13 R242 254

44. ReikWLewisA 2005 Co-evolution of X-chromosome inactivation and imprinting in mammals. Nat Rev Genet 6 403 410

45. WutzARasmussenTPJaenischR 2002 Chromosomal silencing and localization are mediated by different domains of Xist RNA. Nat Genet 30 167 174

46. SmilinichNJDayCDFitzpatrickGVCaldwellGMLossieAC 1999 A maternally methylated CpG island in KvLQT1 is associated with an antisense paternal transcript and loss of imprinting in Beckwith- Wiedemann syndrome. Proc Natl Acad Sci U S A 96 8064 8069

47. MohammadFMondalTGusevaNPandeyGKKanduriC 2010 Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1. Development 137 2493 2499

48. GreenKLewisADawsonCDeanWReinhartB 2007 A developmental window of opportunity for imprinted gene silencing mediated by DNA methylation and the Kcnq1ot1 noncoding RNA. Mamm Genome 18 32 42

49. ZwartRSleutelsFWutzASchinkelAHBarlowDP 2001 Bidirectional action of the Igf2r imprint control element on upstream and downstream imprinted genes. Genes Dev 15 2361 2366

50. CuadradoMSacristanMAntequeraF 2001 Species-specific organization of CpG island promoters at mammalian homologous genes. EMBO Rep 2 586 592

51. FudaNJArdehaliMBLisJT 2009 Defining mechanisms that regulate RNA polymerase II transcription in vivo. Nature 461 186 192

52. BrookesEPomboA 2009 Modifications of RNA polymerase II are pivotal in regulating gene expression states. EMBO Rep 10 1213 1219

53. LevineM 2011 Paused RNA polymerase II as a developmental checkpoint. Cell 145 502 511

54. TianBHuJZhangHLutzCS 2005 A large-scale analysis of mRNA polyadenylation of human and mouse genes. Nucleic Acids Res 33 201 212

55. EdwardsJRO'DonnellAHRollinsRAPeckhamHELeeC 2010 Chromatin and sequence features that define the fine and gross structure of genomic methylation patterns. Genome Res

56. MikkelsenTSKuMJaffeDBIssacBLiebermanE 2007 Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature

57. OoiSKQiuCBernsteinELiKJiaD 2007 DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. Nature 448 714 717

58. ThomsonJPSkenePJSelfridgeJClouaireTGuyJ 2010 CpG islands influence chromatin structure via the CpG-binding protein Cfp1. Nature 464 1082 1086

59. MacleodDCharltonJMullinsJBirdAP 1994 Sp1 sites in the mouse aprt gene promoter are required to prevent methylation of the CpG island. Genes Dev 8 2282 2292

60. BrandeisMFrankDKeshetISiegfriedZMendelsohnM 1994 Sp1 elements protect a CpG island from de novo methylation. Nature 371 435 438

61. DicksonJGowherHStrogantsevRGasznerMHairA 2010 VEZF1 elements mediate protection from DNA methylation. PLoS Genet 6 e1000804 doi:10.1371/journal.pgen.1000804

62. GebhardCBennerCEhrichMSchwarzfischerLSchillingE 2010 General transcription factor binding at CpG islands in normal cells correlates with resistance to de novo DNA methylation in cancer cells. Cancer research 70 1398 1407

63. SmrzkaOWFaeIStogerRKurzbauerRFischerGF 1995 Conservation of a maternal-specific methylation signal at the human IGF2R locus. Hum Mol Genet 4 1945 1952

64. JiaDJurkowskaRZZhangXJeltschAChengX 2007 Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation. Nature 449 248 251

65. ReinhartBPaoloni-GiacobinoAChailletJR 2006 Specific differentially methylated domain sequences direct the maintenance of methylation at imprinted genes. Mol Cell Biol 26 8347 8356

66. GoodrichJATjianR 2010 Unexpected roles for core promoter recognition factors in cell-type-specific transcription and gene regulation. Nat Rev Genet 11 549 558

67. LeeSHChoSYShannonMFFanJRangasamyD 2010 The impact of CpG island on defining transcriptional activation of the mouse L1 retrotransposable elements. PLoS ONE 5 e11353 doi:10.1371/journal.pone.0011353

68. Ramirez-CarrozziVRBraasDBhattDMChengCSHongC 2009 A unifying model for the selective regulation of inducible transcription by CpG islands and nucleosome remodeling. Cell 138 114 128

69. PaulerFMSloaneMAHuangRReghaKKoernerMV 2009 H3K27me3 forms BLOCs over silent genes and intergenic regions and specifies a histone banding pattern on a mouse autosomal chromosome. Genome Res 19 221 233

70. HuangRJaritzMGuenzlPVlatkovicIMSommerA 2011 An RNA-Seq strategy to detect the complete coding and non-coding transcriptome including full-length imprinted macro ncRNAs. PLoS ONE 6 e27288 doi:10.1371/journal.pone.0027288

71. HauserCSchuettengruberBBartlSLaggerGSeiserC 2002 Activation of the mouse histone deacetylase 1 gene by cooperative histone phosphorylation and acetylation. Molecular and cellular biology 22 7820 7830

72. BockCReitherSMikeskaTPaulsenMWalterJ 2005 BiQ Analyzer: visualization and quality control for DNA methylation data from bisulfite sequencing. Bioinformatics 21 4067 4068