title: Sequence and functional comparison in the Beckwith-Wiedemann region: implications for a novel imprinting centre and extended imprinting.
abstract: The clustered organization of most imprinted genes in mammals suggests coordinated genetic and epigenetic control mechanisms. Comparisons between human and mouse will help in elucidating these mechanisms by identifying structural and functional similarities. Previously we reported on such a comparison in the central part of the mouse imprinting cluster on distal chromosome 7 with the homologous Beckwith-Wiedemann syndrome (BWS) gene cluster on human chromosome 11p15.5. Here we focus on the adjacent sequences of 0.5 Mb including the KCNQ1/Kcnq1 and CDKN1C/Cdkn1c genes, which are implicated in BWS, and on one of the proposed boundary regions of the imprinting cluster. As in the previously analysed central region, this part of the cluster exhibits a highly conserved arrangement and structure of genes. The most striking similarity is found in the 3' part of the KCNQ1/Kcnq1 genes in large stretches of mostly non-coding sequences. The conserved region includes the recently identified KCNQ1OT1/Kcnq1ot1 antisense transcripts, flanked by a strikingly conserved cluster of LINE/Line elements and a CpG island which we show to carry a maternal germline methylation imprint. This region is likely to be the proposed second imprinting centre (IC2) in the BWS cluster. We also identified several novel genes inside and outside the previously proposed boundaries of the imprinting cluster. One of the genes outside the cluster, Obph1, is imprinted in mouse placenta indicating that at least in extra-embryonic tissues the imprinting cluster extends into a larger domain.
authors.affiliation: Max-Planck-Institut für Molekulare Genetik, Ihnestrasse 73, D-14195 Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Engemann
authors.forename: M
authors.initials: M
authors.lastname: Strödicke
authors.forename: M
authors.initials: M
authors.lastname: Paulsen
authors.forename: O
authors.initials: O
authors.lastname: Franck
authors.forename: R
authors.initials: R
authors.lastname: Reinhardt
authors.forename: N
authors.initials: N
authors.lastname: Lane
authors.forename: W
authors.initials: W
authors.lastname: Reik
authors.forename: J
authors.initials: J
authors.lastname: Walter
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001506:Beckwith-Wiedemann Syndrome / Q000235:genetics*; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D003001:Cloning, Molecular; D017124:Conserved Sequence / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D050761:Cyclin-Dependent Kinase Inhibitor p57; D005091:Exons / Q000235:genetics; D020224:Expressed Sequence Tags; D005260:Female; D018392:Genomic Imprinting / Q000235:genetics*; D005854:Germ Cells / Q000378:metabolism; D006801:Humans; D007438:Introns / Q000235:genetics; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010920:Placenta / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated; D011987:Receptors, Steroid / Q000737:chemistry / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry / Q000235:genetics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013431:Sulfates / Q000378:metabolism; D000098825:Oxysterol Binding Proteins
chemical_list: C493964:CDKN1C protein, human; C493965:Cdkn1c protein, mouse; D050761:Cyclin-Dependent Kinase Inhibitor p57; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; C496910:Kcnq1 protein, mouse; D009687:Nuclear Proteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011987:Receptors, Steroid; D018124:Receptors, Tumor Necrosis Factor; D013431:Sulfates; D000098825:Oxysterol Binding Proteins; C012036:sodium sulfate