Identification of an imprinted gene cluster in the X-inactivation center

PLoS One. 2013 Aug 6;8(8):e71222. doi: 10.1371/journal.pone.0071222. Print 2013.

Abstract

Mammalian development is strongly influenced by the epigenetic phenomenon called genomic imprinting, in which either the paternal or the maternal allele of imprinted genes is expressed. Paternally expressed Xist, an imprinted gene, has been considered as a single cis-acting factor to inactivate the paternally inherited X chromosome (Xp) in preimplantation mouse embryos. This means that X-chromosome inactivation also entails gene imprinting at a very early developmental stage. However, the precise mechanism of imprinted X-chromosome inactivation remains unknown and there is little information about imprinted genes on X chromosomes. In this study, we examined whether there are other imprinted genes than Xist expressed from the inactive paternal X chromosome and expressed in female embryos at the preimplantation stage. We focused on small RNAs and compared their expression patterns between sexes by tagging the female X chromosome with green fluorescent protein. As a result, we identified two micro (mi)RNAs-miR-374-5p and miR-421-3p-mapped adjacent to Xist that were predominantly expressed in female blastocysts. Allelic expression analysis revealed that these miRNAs were indeed imprinted and expressed from the Xp. Further analysis of the imprinting status of adjacent locus led to the discovery of a large cluster of imprinted genes expressed from the Xp: Jpx, Ftx and Zcchc13. To our knowledge, this is the first identified cluster of imprinted genes in the cis-acting regulatory region termed the X-inactivation center. This finding may help in understanding the molecular mechanisms regulating imprinted X-chromosome inactivation during early mammalian development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blastocyst / metabolism
  • Cloning, Molecular
  • Embryo, Mammalian
  • Female
  • Genomic Imprinting*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • MicroRNAs / genetics
  • Multigene Family*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / isolation & purification
  • X Chromosome / genetics*
  • X Chromosome Inactivation / genetics*

Substances

  • MicroRNAs
  • RNA, Long Noncoding

Grants and funding

This work was supported by the Japan Science and Technology Agency, Precursory Research for Embryonic Science and Technology (PRESTO); a Grant-in-Aid for Scientific Research from The Ministry of Education, Culture, Sports, Science and Technology; and by the Sumitomo Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.