The primate-specific microRNA gene cluster (C19MC) is imprinted in the placenta

被引:253
作者
Noguer-Dance, Marie [1 ,2 ]
Abu-Amero, Sayeda [3 ]
Al-Khtib, Mohamed [4 ]
Lefevre, Annick [4 ]
Coullin, Philippe [5 ]
Moore, Gudrun E. [3 ]
Cavaille, Jerome [1 ,2 ]
机构
[1] Univ Toulouse, Lab Biol Mol Eucaryote, UPS, F-31000 Toulouse, France
[2] CNRS, LBME, F-31000 Toulouse, France
[3] Inst Child Hlth, London WC1N 1EH, England
[4] INSERM, Inst Cellule Souche & Cerveau, U846, F-69008 Lyon, France
[5] Univ Paris 11, INSERM, U782, Clamart, France
基金
英国惠康基金;
关键词
EXPRESSION PATTERNS; DNA METHYLATION; MONOALLELIC EXPRESSION; DOWN-REGULATION; NONCODING RNAS; BRAIN; IDENTIFICATION; EVOLUTION; REGION; ANTISENSE;
D O I
10.1093/hmg/ddq272
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:3566 / 3582
页数:17
相关论文
共 97 条
[1]   Elevated placental expression of the imprinted PHLDA2 gene is associated with low birth weight [J].
Apostolidou, S. ;
Abu-Amero, S. ;
O'Donoghue, K. ;
Frost, J. ;
Olafsdottir, O. ;
Chavele, K. M. ;
Whittaker, J. C. ;
Loughna, P. ;
Stanier, P. ;
Moore, G. F. .
JOURNAL OF MOLECULAR MEDICINE-JMM, 2007, 85 (04) :379-387
[2]   MicroRNA Discovery and Profiling in Human Embryonic Stem Cells by Deep Sequencing of Small RNA Libraries [J].
Bar, Merav ;
Wyman, Stacia K. ;
Fritz, Brian R. ;
Qi, Junlin ;
Garg, Kavita S. ;
Parkin, Rachael K. ;
Kroh, Evan M. ;
Bendoraite, Ausra ;
Mitchell, Patrick S. ;
Nelson, Angelique M. ;
Ruzzo, Walter L. ;
Ware, Carol ;
Radich, Jerald P. ;
Gentleman, Robert ;
Ruohola-Baker, Hannele ;
Tewari, Muneesh .
STEM CELLS, 2008, 26 (10) :2496-2505
[3]   METHYLATION AND IMPRINTING - FROM HOST DEFENSE TO GENE-REGULATION [J].
BARLOW, DP .
SCIENCE, 1993, 260 (5106) :309-310
[4]   Identification of hundreds of conserved and nonconserved human microRNAs [J].
Bentwich, I ;
Avniel, A ;
Karov, Y ;
Aharonov, R ;
Gilad, S ;
Barad, O ;
Barzilai, A ;
Einat, P ;
Einav, U ;
Meiri, E ;
Sharon, E ;
Spector, Y ;
Bentwich, Z .
NATURE GENETICS, 2005, 37 (07) :766-770
[5]   SNP-specific array-based allele-specific expression analysis [J].
Bjornsson, Hans T. ;
Albert, Thomas J. ;
Ladd-Acosta, Christine M. ;
Green, Roland D. ;
Rongione, Michael A. ;
Middle, Christina M. ;
Irizarry, Rafael A. ;
Broman, Karl W. ;
Feinberg, Andrew P. .
GENOME RESEARCH, 2008, 18 (05) :771-779
[6]   RNA polymerase III transcribes human microRNAs [J].
Borchert, Glen M. ;
Lanier, William ;
Davidson, Beverly L. .
NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2006, 13 (12) :1097-1101
[7]   C19MC microRNAs are processed from introns of large Pol-II, non-protein-coding transcripts [J].
Bortolin-Cavaille, Marie-Line ;
Dance, Marie ;
Weber, Michel ;
Cavaille, Jerome .
NUCLEIC ACIDS RESEARCH, 2009, 37 (10) :3464-3473
[8]   Origins of extreme sexual dimorpism in genomic imprinting [J].
Bourc'his, D. ;
Bestor, T. H. .
CYTOGENETIC AND GENOME RESEARCH, 2006, 113 (1-4) :36-40
[9]   C15orf2 and a novel noncoding transcript from the Prader-Willi/Angelman syndrome region show monoallelic expression in fetal brain [J].
Buiting, Karin ;
Nazlican, Huelya ;
Galetzka, Danuta ;
Wawrzik, Michaela ;
Gross, Stephanie ;
Horsthemke, Bernhard .
GENOMICS, 2007, 89 (05) :588-595
[10]   Genomic imprinting disorders in humans: a mini-review [J].
Butler, Merlin G. .
JOURNAL OF ASSISTED REPRODUCTION AND GENETICS, 2009, 26 (9-10) :477-486