Abstract
Gene expression profiling was performed on central nervous system (CNS) tissue from neonatal mice carrying the T9H translocation and maternal or paternal duplication of proximal Chromosomes 7 and 15. Our analysis revealed the presence of two novel paternally expressed intergenic transcripts at the Prader–Willi/Angelman Syndrome (PW/AS) locus. The transcripts were termed Pec2 and Pec3, for paternally expressed in the CNS. Imprinting of these transcripts was confirmed by sequencing of RT-PCR products in F1 hybrids between Mus musculus musculus C57BL/6 and Mus musculus castaneus, following identification of single nucleotide polymorphisms between the two strains. Imprinting of Pec2 was also confirmed by Northern blot analysis. The two transcripts are separated by 0.5 Mb and are transcribed in the same orientation. They are located in a long interspersed transposable element (LINE)-rich region midway between the PW/AS imprinting center and the paternally expressed genes Ndn, Magel2, and Mkrn3, which are under imprinting center control. Our analysis also revealed imprinting of Magel2, Mkrn3, Ndn, Ube3a, and Usp29, as well as Pec2 and Pec3, in embryonic brain 15.5 dpc, and provided a survey of biallelically expressed genes on proximal Chrs 7 and 15 in embryonic and neonatal CNS.
Similar content being viewed by others
References
U Albrecht JS Sutcliffe BM Cattanach CV Beechey D Armstrong et al. (1997) ArticleTitleImprinted expression of the murine Angelman syndrome gene, Ube3a, in hippocampal and Purkinje neurons Nat Genet 17 75–78 Occurrence Handle1:CAS:528:DyaK2sXlvVGht70%3D Occurrence Handle9288101
E Allen S Horvath F Tong P Kraft E Spiteri et al. (2003) ArticleTitleHigh concentrations of long interspersed nuclear element sequence distinguish monoallelically expressed genes Proc Natl Acad Sci USA 100 9940–9945 Occurrence Handle1:CAS:528:DC%2BD3sXmvVeju70%3D Occurrence Handle12909712
HL Ashe J Monks M Wijgerde P Fraser NJ Proudfoot (1997) ArticleTitleIntergenic transcription and transinduction of the human beta-globin locus Genes Dev 11 2494–2509 Occurrence Handle1:CAS:528:DyaK2sXmslajtr0%3D Occurrence Handle9334315
B Bielinska SM Blaydes K Buiting T Yang M Krajewska–Walasek et al. (2000) ArticleTitleDe 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 Occurrence Handle1:CAS:528:DC%2BD3cXjtFSltrY%3D Occurrence Handle10802660
I Boccaccio H Glatt–Deeley F Watrin N Roeckel M Lalande et al. (1999) ArticleTitleThe human MAGEL2 gene and its mouse homologue are paternally expressed and mapped to the Prader–Willi region Hum Mol Genet 8 2497–2505 Occurrence Handle1:CAS:528:DyaK1MXnvFKrurs%3D Occurrence Handle10556298
VL Buettner JM LeBon C Gao AD Riggs J Singer–Sam (2000) ArticleTitleUse of terminal transferase-dependent antisense RNA amplification to determine the transcription start site of the Snrpn gene in individual neurons Nucleic Acids Res 28 E25 Occurrence Handle1:CAS:528:DC%2BD3cXmtlCisrY%3D Occurrence Handle10710442
VL Buettner JA Longmate ME Barish JR Mann J Singer–Sam (2004) ArticleTitleAnalysis of imprinting in mice with uniparental duplication of proximal chromosomes 7 and 15 by use of a custom oligonucleotide microarray Mamm Genome 15 199–209 Occurrence Handle1:CAS:528:DC%2BD2cXitVOhsrY%3D Occurrence Handle15014969
K Buiting C Lich S Cottrell A Barnicoat B Horsthemke (1999) ArticleTitleA 5-kb imprinting center deletion in a family with Angelman syndrome reduces the shortest region of deletion overlap to 880 bp Hum Genet 105 665–666 Occurrence Handle1:CAS:528:DC%2BD3cXhtFOrs74%3D Occurrence Handle10647904
J Cavaille K Buiting M Kiefmann M Lalande CI Brannan et al. (2000) ArticleTitleIdentification of brain-specific and imprinted small nucleolar RNA genes exhibiting unusual genomic organization Proc Natl Acad Sci USA 97 14311–14316 Occurrence Handle1:CAS:528:DC%2BD3MXitVCltg%3D%3D Occurrence Handle11106375
SJ Chamberlain CI Brannan (2001) ArticleTitleThe Prader–Willi syndrome imprinting center activates the paternally expressed murine Ube3a antisense transcript but represses paternal Ube3a Genomics 73 316–322 Occurrence Handle1:CAS:528:DC%2BD3MXjtlGgsb4%3D Occurrence Handle11350123
T los Santos Particlede J Schweizer CA Rees U Francke (2000) ArticleTitleSmall evolutionarily conserved RNA, resembling C/D box small nucleolar RNA, is transcribed from PWCR1, a novel imprinted gene in the Prader–Willi deletion region, which is highly expressed in brain Am J Hum Genet 67 1067–1082 Occurrence Handle11007541
RM Fourney J Miyakoshi RS Day SuffixIII MC Paterson (1988) ArticleTitleNorthern blotting: efficient RNA staining and transfer BRL Focus 10 IssueID1 5–7
CC Glenn KA Porter MT Jong RD Nicholls DJ Driscoll (1993) ArticleTitleFunctional imprinting and epigenetic modification of the human SNRPN gene Hum Mol Genet 2 2001–2005 Occurrence Handle1:CAS:528:DyaK2cXntVOksg%3D%3D Occurrence Handle8111367
TA Gray S Saitoh RD Nicholls (1999) ArticleTitleAn imprinted, mammalian bicistronic transcript encodes two independent proteins Proc Natl Acad Sci USA 96 5616–5621 Occurrence Handle1:CAS:528:DyaK1MXjtFCnt7g%3D Occurrence Handle10318933
JM Greally (2002) ArticleTitleShort interspersed transposable elements (SINEs) are excluded from imprinted regions in the human genome Proc Natl Acad Sci USA 99 327–332 Occurrence Handle1:CAS:528:DC%2BD38Xlt1Clsw%3D%3D Occurrence Handle11756672
J Gribnau K Diderich S Pruzina R Calzolari P Fraser (2000) ArticleTitleIntergenic transcription and developmental remodeling of chromatin subdomains in the human beta-globin locus Mol Cell 5 377–386 Occurrence Handle1:CAS:528:DC%2BD3cXhslyhtb4%3D Occurrence Handle10882078
Y Hayashizaki H Shibata S Hirotsune H Sugino Y Okazaki et al. (1994) ArticleTitleIdentification of an imprinted U2af binding protein related sequence on mouse chromosome 11 using the RLGS method Nat Genet 6 33–40 Occurrence Handle10.1038/ng0194-33 Occurrence Handle1:CAS:528:DyaK2cXis1amsLc%3D Occurrence Handle8136831
A Hershko A Razin R Shemer (1999) ArticleTitleImprinted methylation and its effect on expression of the mouse Zfp127 gene Gene 234 323–327 Occurrence Handle1:CAS:528:DyaK1MXks1Cqtrc%3D Occurrence Handle10395905
P Jay C Rougeulle A Massacrier A Moncla MG Mattei et al. (1997) ArticleTitleThe human necdin gene, NDN, is maternally imprinted and located in the Prader–Willi syndrome chromosomal region Nat Genet 17 357–361 Occurrence Handle1:CAS:528:DyaK2sXntVWisrY%3D Occurrence Handle9354807
RM John MA Surani (2000) ArticleTitleGenomic imprinting, mammalian evolution, and the mystery of egg-laying mammals Cell 101 585–588 Occurrence Handle1:CAS:528:DC%2BD3cXkt1Wrsbc%3D Occurrence Handle10892645
MT Jong TA Gray Y Ji CC Glenn S Saitoh et al. (1999) ArticleTitleA novel imprinted gene, encoding a RING zinc-finger protein, and overlapping antisense transcript in the Prader–Willi syndrome critical region Hum Mol Genet 8 783–793 Occurrence Handle1:CAS:528:DyaK1MXivFamsbg%3D Occurrence Handle10196367
EB Keverne R Fundele M Narasimha SC Barton MA Surani (1996) ArticleTitleGenomic imprinting and the differential roles of parental genomes in brain development Brain Res Dev Brain Res 92 91–100 Occurrence Handle1:CAS:528:DyaK28XitFCisL8%3D Occurrence Handle8861727
Y Kuroiwa T Kaneko–Ishino F Kagitani T Kohda LL Li et al. (1996) ArticleTitlePeg3 imprinted gene on proximal chromosome 7 encodes for a zinc finger protein Nat Genet 12 186–190 Occurrence Handle1:CAS:528:DyaK28XosFCmug%3D%3D Occurrence Handle8563758
JT Lee LS Davidow D Warshawsky (1999) ArticleTitleTsix, a gene antisense to Xist at the X-inactivation centre Nat Genet 21 400–404 Occurrence Handle1:CAS:528:DyaK1MXitFKrs7c%3D Occurrence Handle10192391
SE Leff CI Brannan ML Reed T Ozcelik U Francke et al. (1992) ArticleTitleMaternal imprinting of the mouse Snrpn gene and conserved linkage homology with the human Prader–Willi syndrome region Nat Genet 2 259–264 Occurrence Handle1:CAS:528:DyaK3sXpsFeqtg%3D%3D Occurrence Handle1303276
LL Li IY Szeto BM Cattanach F Ishino MA Surani (2000) ArticleTitleOrganization and parent-of-origin-specific methylation of imprinted Peg3 gene on mouse proximal chromosome 7 Genomics 63 333–340 Occurrence Handle1:CAS:528:DC%2BD3cXhsFShtrw%3D Occurrence Handle10704281
HR MacDonald R Wevrick (1997) ArticleTitleThe necdin gene is deleted in Prader–Willi syndrome and is imprinted in human and mouse Hum Mol Genet 6 1873–1878 Occurrence Handle1:CAS:528:DyaK2sXmslGrtL0%3D Occurrence Handle9302265
M Meguro K Mitsuya N Nomura M Kohda A Kashiwagi et al. (2001) ArticleTitleLarge-scale evaluation of imprinting status in the Prader–Willi syndrome region: an imprinted direct repeat cluster resembling small nucleolar RNA genes Hum Mol Genet 10 383–394 Occurrence Handle1:CAS:528:DC%2BD3MXhsVygtrs%3D Occurrence Handle11157801
RD Nicholls JL Knepper (2001) ArticleTitleGenome organization, function, and imprinting in Prader–Willi and Angelman syndromes Annu Rev Genomics Hum Genet 2 153–175 Occurrence Handle1:CAS:528:DC%2BD3MXos1antb8%3D Occurrence Handle11701647
T Ohta K Buiting H Kokkonen S McCandless S Heeger et al. (1999) ArticleTitleMolecular mechanism of Angelman syndrome in two large families involves an imprinting mutation Am J Hum Genet 64 385–396 Occurrence Handle1:CAS:528:DyaK1MXhslOlt7k%3D Occurrence Handle9973277
T Ozcelik S Leff W Robinson T Donlon M Lalande et al. (1992) ArticleTitleSmall nuclear ribonucleoprotein polypeptide N (SNRPN), an expressed gene in the Prader–Willi syndrome critical region Nat Genet 2 265–269 Occurrence Handle1:CAS:528:DyaK3sXpsFeqtw%3D%3D Occurrence Handle1303277
J Peters C Beechey (2004) ArticleTitleIdentification and characterisation of imprinted genes in the mouse Brief Funct Genomic Proteomic 2 320–333 Occurrence Handle1:CAS:528:DC%2BD2cXjtFyrtro%3D Occurrence Handle15163367
DF Rogan DJ Cousins DZ Staynov (1999) ArticleTitleIntergenic transcription occurs throughout the human IL-4/IL-13 gene cluster Biochem Biophys Res Commun 255 556–561 Occurrence Handle1:CAS:528:DyaK1MXhtlCiurc%3D Occurrence Handle10049749
DF Rogan DJ Cousins S Santangelo PA Ioannou M Antoniou et al. (2004) ArticleTitleAnalysis of intergenic transcription in the human IL-4/IL-13 gene cluster Proc Natl Acad Sci USA 101 2446–2451 Occurrence Handle1:CAS:528:DC%2BD2cXhvVOisbc%3D Occurrence Handle14983029
C Rougeulle H Glatt M Lalande (1997) ArticleTitleThe Angelman syndrome candidate gene, UBE3A/E6-AP, is imprinted in brain Nat Genet 17 14–15 Occurrence Handle1:CAS:528:DyaK2sXlvVCktbc%3D Occurrence Handle9288088
C Rougeulle C Cardoso M Fontes L Colleaux M Lalande (1998) ArticleTitleAn imprinted antisense RNA overlaps UBE3A and a second maternally expressed transcript Nat Genet 19 15–16 Occurrence Handle1:CAS:528:DyaK1cXislWqur0%3D Occurrence Handle9590281
M Runte A Huttenhofer S Gross M Kiefmann B Horsthemke et al. (2001) ArticleTitleThe IC-SNURF-SNRPN transcript serves as a host for multiple small nucleolar RNA species and as an antisense RNA for UBE3A Hum Mol Genet 10 2687–2700 Occurrence Handle1:CAS:528:DC%2BD3MXptFGhurs%3D Occurrence Handle11726556
AG Searle CV Beechey (1990) ArticleTitleGenome imprinting phenomena on mouse chromosome 7 Genet Res 56 237–244 Occurrence Handle1:STN:280:By6C3cnns1c%3D Occurrence Handle2272514
R Shemer Y Birger AD Riggs A Razin (1997) ArticleTitleStructure of the imprinted mouse Snrpn gene and establishment of its parental-specific methylation pattern Proc Natl Acad Sci USA 94 10267–10272 Occurrence Handle1:CAS:528:DyaK2sXmt1GjsL8%3D Occurrence Handle9294199
F Sleutels R Zwart DP Barlow (2002) ArticleTitleThe non-coding Air RNA is required for silencing autosomal imprinted genes Nature 415 810–813 Occurrence Handle1:CAS:528:DC%2BD38XhsFersrw%3D Occurrence Handle11845212
D Solter (1988) ArticleTitleDifferential imprinting and expression of maternal and paternal genomes Annu Rev Genet 22 127–146 Occurrence Handle1:CAS:528:DyaL1MXht12gsLg%3D Occurrence Handle3071246
DF Swaab (1997) ArticleTitlePrader–Willi syndrome and the hypothalamus Acta Paediatr Suppl 423 50–54 Occurrence Handle1:STN:280:DyaK1c%2FmsFSlsw%3D%3D Occurrence Handle9401539
TH Vu AR Hoffman (1997) ArticleTitleImprinting of the Angelman syndrome gene, UBE3A, is restricted to brain Nat Genet 17 12–13 Occurrence Handle1:CAS:528:DyaK2sXlvVCktbY%3D Occurrence Handle9288087
F Watrin N Roeckel L Lacroix C Mignon MG Mattei et al. (1997) ArticleTitleThe mouse Necdin gene is expressed from the paternal allele only and lies in the 7C region of the mouse chromosome 7, a region of conserved synteny to the human Prader–Willi syndrome region Eur J Hum Genet 5 324–332 Occurrence Handle1:CAS:528:DyaK2sXnvF2qs7s%3D Occurrence Handle9412790
R Wevrick U Francke (1997) ArticleTitleAn imprinted mouse transcript homologous to the human imprinted in Prader–Willi syndrome (IPW) gene Hum Mol Genet 6 325–332 Occurrence Handle1:CAS:528:DyaK2sXht1altro%3D Occurrence Handle9063754
T Yang TE Adamson JL Resnick S Left R Wevrick et al. (1998) ArticleTitleA mouse model for Prader–Willi syndrome imprinting-centre mutations Nat Genet 19 25–31 Occurrence Handle1:CAS:528:DyaK1cXislWqurg%3D Occurrence Handle9590284
Acknowledgments
We thank Jeff Mann for kindly providing T9H mouse stocks. This work was supported by NIH NINDS grant RO1 NS39645.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Buettner, V.L., Walker, A.M. & Singer–Sam, J. Novel paternally expressed intergenic transcripts at the mouse Prader–Willi/Angelman Syndrome locus. Mamm Genome 16, 219–227 (2005). https://doi.org/10.1007/s00335-004-2452-7
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s00335-004-2452-7