title: Identification of the human homolog of the imprinted mouse Air non-coding RNA.
abstract: Genomic imprinting is widely conserved amongst placental mammals. Imprinted expression of IGF2R, however, differs between mice and humans. In mice, Igf2r imprinted expression is seen in all fetal and adult tissues. In humans, adult tissues lack IGF2R imprinted expression, but it is found in fetal tissues and Wilms' tumors where it is polymorphic and only seen in a small proportion of tested samples. Mouse Igf2r imprinted expression is controlled by the Air (Airn) ncRNA whose promoter lies in an intronic maternally-methylated CpG island. The human IGF2R gene carries a homologous intronic maternally-methylated CpG island of unknown function. Here, we use transfection and transgenic studies to show that the human IGF2R intronic CpG island is a ncRNA promoter. We also identify the same ncRNA at the endogenous human locus in 16-40% of Wilms' tumors. Thus, the human IGF2R gene shows evolutionary conservation of key features that control imprinted expression in the mouse.
authors.affiliation: Ce-M-M-Research Center for Molecular Medicine of the Austrian Academy of Science, Vienna Biocenter, Dr. Bohr-Gasse 9/4, A1030 Vienna, Austria.
authors.forename: Iveta Y
authors.initials: IY
authors.lastname: Yotova
authors.forename: Irena M
authors.initials: IM
authors.lastname: Vlatkovic
authors.forename: Florian M
authors.initials: FM
authors.lastname: Pauler
authors.forename: Katarzyna E
authors.initials: KE
authors.lastname: Warczok
authors.forename: Peter F
authors.initials: PF
authors.lastname: Ambros
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Oshimura
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Theussl
authors.forename: Manfred
authors.initials: M
authors.lastname: Gessler
authors.forename: Erwin F
authors.initials: EF
authors.lastname: Wagner
authors.forename: Denise P
authors.initials: DP
authors.lastname: Barlow
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D018899:CpG Islands; D019175:DNA Methylation; D019143:Evolution, Molecular; D015870:Gene Expression; D018392:Genomic Imprinting; D006367:HeLa Cells; D006801:Humans; D007438:Introns; D051379:Mice; D008822:Mice, Transgenic; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D022661:RNA, Untranslated / Q000235:genetics*; D017527:Receptor, IGF Type 2 / Q000235:genetics*; D024363:Transcription Initiation Site; D014162:Transfection; D019076:Transgenes; D009396:Wilms Tumor / Q000235:genetics
chemical_list: D022661:RNA, Untranslated; D017527:Receptor, IGF Type 2
references.citation: Nature. 2008 Jan 10;451(7175):202-6
references.pmid: 18185590
references.citation: Nature. 1997 Oct 16;389(6652):745-9
references.pmid: 9338788
references.citation: Trends Genet. 2005 Aug;21(8):457-65
references.pmid: 15990197
references.citation: Genes Dev. 2001 Sep 15;15(18):2361-6
references.pmid: 11562346
references.citation: Cell Mol Life Sci. 2003 Aug;60(8):1647-58
references.pmid: 14504655
references.citation: Nat Genet. 2003 Jun;34(2):157-65
references.pmid: 12730694
references.citation: Genes Chromosomes Cancer. 2003 May;37(1):29-35
references.pmid: 12661003
references.citation: EMBO J. 2006 Aug 9;25(15):3565-75
references.pmid: 16874305
references.citation: Mol Cell Biol. 2001 Aug;21(15):5008-17
references.pmid: 11438657
references.citation: Cell. 2008 Jan 25;132(2):311-22
references.pmid: 18243105
references.citation: Nat Genet. 1993 Sep;5(1):74-8
references.pmid: 8220428
references.citation: Genomics. 2001 May 1;73(3):331-7
references.pmid: 11350125
references.citation: Cancer Res. 2005 Dec 15;65(24):11236-40
references.pmid: 16357124
references.citation: DNA Res. 1999 Jun 30;6(3):165-72
references.pmid: 10470847
references.citation: Nat Biotechnol. 2001 May;19(5):440-5
references.pmid: 11329013
references.citation: Genome Res. 2005 Oct;15(10):1379-87
references.pmid: 16204191
references.citation: Nature. 1993 Nov 25;366(6453):362-5
references.pmid: 8247133
references.citation: Oncogene. 1997 Mar 6;14(9):1041-6
references.pmid: 9070652
references.citation: Nature. 2002 Feb 14;415(6873):810-3
references.pmid: 11845212
references.citation: Br J Cancer. 1997;76(12):1558-61
references.pmid: 9413941
references.citation: Nat Genet. 2000 May;25(1):19-21
references.pmid: 10802648
references.citation: Genomics. 1996 Jan 15;31(2):158-66
references.pmid: 8824797
references.citation: Dev Biol. 2006 Oct 15;298(2):344-53
references.pmid: 16916508
references.citation: Genes Chromosomes Cancer. 2003 Sep;38(1):40-52
references.pmid: 12874785
references.citation: Genes Dev. 1995 Aug 1;9(15):1857-68
references.pmid: 7649473
references.citation: Hum Mol Genet. 2001 Aug 15;10(17):1721-8
references.pmid: 11532981
references.citation: Cytogenet Genome Res. 2006;113(1-4):202-8
references.pmid: 16575181
references.citation: Nucleic Acids Res. 2006 Jan 23;34(2):555-63
references.pmid: 16432260
references.citation: Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1412-7
references.pmid: 16432200
references.citation: Cytogenet Genome Res. 2006;113(1-4):12-6
references.pmid: 16575157
references.citation: Hum Mol Genet. 2005 Sep 1;14(17):2511-20
references.pmid: 16037066
references.citation: Placenta. 2004 Apr;25 Suppl A:S10-5
references.pmid: 15033301
references.citation: Biochem Biophys Res Commun. 1993 Dec 15;197(2):747-54
references.pmid: 8267611
references.citation: Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6623-8
references.pmid: 16614068
references.citation: Hum Mol Genet. 2003 Jul 1;12(13):1569-78
references.pmid: 12812984
references.citation: Nature. 1994 Dec 1;372(6505):464-7
references.pmid: 7984240
references.citation: Nat Rev Mol Cell Biol. 2003 Mar;4(3):202-12
references.pmid: 12612639
references.citation: Adv Cancer Res. 2008;99:77-112
references.pmid: 18037407
references.citation: Hum Mol Genet. 1993 Dec;2(12):2163-5
references.pmid: 8111387
references.citation: Cold Spring Harb Symp Quant Biol. 2004;69:55-66
references.pmid: 16117633
references.citation: Cytogenet Genome Res. 2006;113(1-4):165-77
references.pmid: 16575177
references.citation: Breast Cancer Res Treat. 1998 Feb;47(3):269-81
references.pmid: 9516081
references.citation: Hum Mol Genet. 1995 Oct;4(10):1945-52
references.pmid: 8595419