A large imprinted microRNA gene cluster at the mouse Dlk1-Gtl2 domain.
microRNAs (or miRNAs) are small noncoding RNAs (21 to 25 nucleotides) that are processed from longer hairpin RNA precursors and are believed to be involved in a wide range of developmental and cellular processes, by either repressing translation or triggering mRNA degradation (RNA interference). By using a computer-assisted approach, we have identified 46 potential miRNA genes located in the human imprinted 14q32 domain, 40 of which are organized as a large cluster. Although some of these clustered miRNA genes appear to be encoded by a single-copy DNA sequence, most of them are arranged in tandem arrays of closely related sequences. In the mouse, this miRNA gene cluster is conserved at the homologous distal 12 region. In vivo all the miRNAs that we have detected are expressed in the developing embryo (both in the head and in the trunk) and in the placenta, whereas in the adult their expression is mainly restricted to the brain. We also show that the miRNA genes are only expressed from the maternally inherited chromosome and that their imprinted expression is regulated by an intergenic germline-derived differentially methylated region (IG-DMR) located approximately 200 kb upstream from the miRNA cluster. The functions of these miRNAs, which seem only conserved in mammals, are discussed both in terms of epigenetic control and gene regulation during development.
Seitz
Hervé
H
LBME-CNRS (UMR 5099), IFR-109, Université P. Sabatier, 31062 Toulouse, France.
Royo
Hélène
H
Bortolin
Marie-Line
ML
Lin
Shau-Ping
SP
Ferguson-Smith
Anne C
AC
Cavaillé
Jérôme
J
D000818:Animals; D001483:Base Sequence; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D019295:Computational Biology; D017124:Conserved Sequence; D019175:DNA Methylation; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting; D006801:Humans; D040582:Inheritance Patterns; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D011506:Proteins / Q000235:genetics*; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012689:Sequence Homology, Nucleic Acid
D047908:Intracellular Signaling Peptides and Proteins; C498907:MEG3 non-coding RNA, human; C422882:MEG3 non-coding RNA, mouse; D008565:Membrane Proteins; D035683:MicroRNAs; D011506:Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C064045:delta protein