title: The primate-specific microRNA gene cluster (C19MC) is imprinted in the placenta.
abstract: Imprinted genes play crucial roles in mammalian development and disruption of their expression is associated with many human disorders including tumourigenesis; yet, the actual number of imprinted genes in the human genome remains a matter of debate. Here, we report on the unexpected finding that the chromosome 19 microRNA cluster (C19MC), the largest human microRNA gene cluster discovered so far, is regulated by genomic imprinting with only the paternally inherited allele being expressed in the placenta. DNA methylation profiling identified a differentially methylated region (C19MC-DMR1) that overlaps an upstream CpG-rich promoter region associated with short tandem repeats. It displays a maternal-specific methylation imprint acquired in oocytes and generates a complex population of large, compartimentalized non-coding RNA (ncRNA) species retained in close proximity to the C19MC transcription site. This occurs adjacent to, but not within, a poorly characterized nuclear Alu-rich domain. Interestingly, C19MC maps near another imprinted gene, the maternally expressed ZNF331 gene, and therefore may define a novel, previously unrecognized large imprinted primate-specific chromosomal domain. Altogether, our study adds C19MC to the growing list of imprinted repeated small RNA gene clusters and further strengthens the potential involvement of small ncRNAs in the function and/or the evolution of imprinted gene networks.
authors.affiliation: Laboratoire de Biologie Moléculaire Eucaryote, Université de Toulouse, Toulouse, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Noguer-Dance
authors.forename: Sayeda
authors.initials: S
authors.lastname: Abu-Amero
authors.forename: Mohamed
authors.initials: M
authors.lastname: Al-Khtib
authors.forename: Annick
authors.initials: A
authors.lastname: Lefèvre
authors.forename: Philippe
authors.initials: P
authors.lastname: Coullin
authors.forename: Gudrun E
authors.initials: GE
authors.lastname: Moore
authors.forename: Jérôme
authors.initials: J
authors.lastname: Cavaillé
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D018392:Genomic Imprinting; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011323:Primates / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016415:Sequence Alignment; D013045:Species Specificity
chemical_list: D035683:MicroRNAs