Re-investigation and RNA sequencing-based identification of genes with placenta-specific imprinted expression

Hum Mol Genet. 2012 Feb 1;21(3):548-58. doi: 10.1093/hmg/ddr488. Epub 2011 Oct 24.


Within the vertebrate groups, only mammals are subject to a specialized epigenetic process termed genomic imprinting in which genes are preferentially expressed from one parental allele. Imprinted expression has been reported for >100 mouse genes and, for approximately one-quarter of these genes, the imprinted expression is specific to the placenta (or extraembryonic tissues). This seemingly placenta-specific imprinted expression has garnered much attention, as has the apparent lack of conserved imprinting between the human and mouse placenta. In this study, we used a novel approach to re-investigate the placenta-specific expression using embryo transfer and trophoblast stem cells. We analyzed 20 genes previously reported to show maternal allele-specific expression in the placenta, and only 8 genes were confirmed to be imprinted. Other genes were likely to be falsely identified as imprinted due to their relatively high expression in contaminating maternal cells. Next, we performed a genome-wide transcriptome assay and identified 133 and 955 candidate imprinted genes with paternal allele- and maternal allele-specific expression. Of those we analyzed in detail, 1/6 (Gab1) of the candidates for paternal allele-specific expression and only 1/269 (Ano1) candidates for maternal allele-specific expression were authentically imprinted genes. Imprinting of Ano1 and Gab1 was specific to the placenta and neither gene displayed allele-specific promoter DNA methylation. Imprinting of ANO1, but not GAB1, was conserved in the human placenta. Our findings impose a considerable revision of the current views of placental imprinting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Alleles
  • Animals
  • Anoctamin-1
  • Chloride Channels / genetics*
  • Chloride Channels / metabolism
  • Decidua / metabolism
  • Embryo Transfer
  • Female
  • Gene Expression Profiling
  • Genomic Imprinting*
  • Humans
  • Mice
  • Phosphoproteins / genetics
  • Placenta / metabolism*
  • Pregnancy
  • Repressor Proteins
  • Sequence Analysis, RNA
  • Stem Cells / cytology
  • Transcription Factors / genetics
  • Trophoblasts / cytology


  • ANO1 protein, mouse
  • Adaptor Proteins, Signal Transducing
  • Anoctamin-1
  • Chloride Channels
  • Gab1 protein, mouse
  • Phosphoproteins
  • Repressor Proteins
  • Sfmbt2 protein, mouse
  • Transcription Factors