Identification of novel imprinted genes in a genome-wide screen for maternal methylation

Genome Res. 2003 Apr;13(4):558-69. doi: 10.1101/gr.781503.


A characteristic of imprinted genes is that the maternal and paternal alleles show differences in methylation. To perform a genome-wide screen for novel imprinted loci, we applied methylation-sensitive representational difference analysis (Me-RDA) to parthenogenetic mouse embryos, to identify differentially methylated regions (DMRs) methylated specifically on the maternal allele. We isolated a total of 26 distinct clones from known and novel DMRs and identified three novel imprinted genes. Nap1l5 is located on proximal chromosome 6 and encodes a protein with homology with nucleosome assembly proteins (NAPs); it has tissue-specific imprinting with expression from the paternal allele. We identified two DMRs on chromosome 15, a chromosome that was not thought to contain imprinted loci, and demonstrated that each is associated with a paternally expressed transcript. Peg13 gives rise to a noncoding RNA that is highly expressed in the brain and imprinted in all tissues examined. A DMR was also identified at the chromosome 15 Slc38a4 gene, which encodes a system A amino acid transporter; we show that Slc38a4 is imprinted in a tissue-specific manner. Interestingly, two of the three novel genes identified in this screen are located within the introns of other genes; their identification indicates that such "microimprinted" domains may be more common than previously thought.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Transport System A / genetics
  • Animals
  • Cell Cycle Proteins
  • Chromosome Mapping / methods
  • CpG Islands / genetics
  • DNA Methylation*
  • Embryo, Mammalian
  • Female
  • Gene Expression Regulation, Developmental / genetics
  • Genetic Testing / methods*
  • Genome*
  • Genomic Imprinting / genetics*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Molecular Sequence Data
  • Nuclear Proteins
  • Nucleosome Assembly Protein 1
  • Nucleosomes / genetics
  • Proteins / genetics
  • RNA, Messenger, Stored / genetics
  • Rats
  • Sequence Homology, Nucleic Acid


  • Amino Acid Transport System A
  • Cell Cycle Proteins
  • NAP1L1 protein, human
  • Nap1l1 protein, mouse
  • Nap1l1 protein, rat
  • Nuclear Proteins
  • Nucleosome Assembly Protein 1
  • Nucleosomes
  • Proteins
  • RNA, Messenger, Stored
  • Slc38a4 protein, mouse
  • Slc38a4 protein, rat

Associated data

  • GENBANK/AY151252
  • GENBANK/AY151253