title: Conservation of the H19 noncoding RNA and H19-IGF2 imprinting mechanism in therians.
abstract: Comparisons between eutherians and marsupials suggest limited conservation of the molecular mechanisms that control genomic imprinting in mammals. We have studied the evolution of the imprinted IGF2-H19 locus in therians. Although marsupial orthologs of protein-coding exons were easily identified, the use of evolutionarily conserved regions and low-stringency Bl2seq comparisons was required to delineate a candidate H19 noncoding RNA sequence. The therian H19 orthologs show miR-675 and exon structure conservation, suggesting functional selection on both features. Transcription start site sequences and poly(A) signals are also conserved. As in eutherians, marsupial H19 is maternally expressed and paternal methylation upstream of the gene originates in the male germline, encompasses a CTCF insulator, and spreads somatically into the H19 gene. The conservation in all therians of the mechanism controlling imprinting of the IGF2-H19 locus suggests a sequential model of imprinting evolution.
authors.affiliation: The Babraham Institute, Laboratory of Developmental Genetics and Imprinting, Cambridge CB22 3AT, UK.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Smits
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Mungall
authors.forename: Sam
authors.initials: S
authors.lastname: Griffiths-Jones
authors.forename: Paul
authors.initials: P
authors.lastname: Smith
authors.forename: Delphine
authors.initials: D
authors.lastname: Beury
authors.forename: Lucy
authors.initials: L
authors.lastname: Matthews
authors.forename: Jane
authors.initials: J
authors.lastname: Rogers
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Pask
authors.forename: Geoff
authors.initials: G
authors.lastname: Shaw
authors.forename: John L
authors.initials: JL
authors.lastname: VandeBerg
authors.forename: John R
authors.initials: JR
authors.lastname: McCarrey
authors.forename: Marilyn B
authors.initials: MB
authors.lastname: Renfree
authors.forename: Wolf
authors.initials: W
authors.lastname: Reik
authors.forename: Ian
authors.initials: I
authors.lastname: Dunham
mesh_terms: D000818:Animals; D001483:Base Sequence; D019175:DNA Methylation; D019143:Evolution, Molecular; D005260:Female; D018392:Genomic Imprinting; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D007614:Macropodidae / Q000235:genetics*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment
chemical_list: C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D007335:Insulin-Like Growth Factor II