Journal Article

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

Marie Noguer-Dance, Sayeda Abu-Amero, Mohamed Al-Khtib, Annick Lefèvre, Philippe Coullin, Gudrun E. Moore and Jérôme Cavaillé

in Human Molecular Genetics

Volume 19, issue 18, pages 3566-3582
Published in print September 2010 | ISSN: 0964-6906
Published online July 2010 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddq272
The primate-specific microRNA gene cluster (C19MC) is imprinted in the placenta

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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.

Journal Article.  9281 words.  Illustrated.

Subjects: Genetics and Genomics

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