Methylation analysis of the intergenic differentially methylated region of DLK1-GTL2 in human

Eur J Hum Genet. 2007 Mar;15(3):352-61. doi: 10.1038/sj.ejhg.5201759. Epub 2007 Jan 10.


Imprinting is a non-Mendelian form of inheritance where epigenetic modifications control mono-allelic expression depending on the parental origin. Methylation of CpG-dinucleotides at differentially methylated regions (DMRs) is one of the best-studied mechanisms directing expression to one specific parental allele. We studied the methylation patterns of the intergenic (IG)-DMR of DLK1 and GTL2. The methylation marks of the IG-DMR were analysed in human gametes, preimplantation embryos, amniocytes and blood of babies born after intracytoplasmic sperm injection (ICSI) and blood from adults using a bisulphite sequencing technique. In oocytes, the IG-DMR was mainly unmethylated while in sperm cells a generally methylated pattern was detected. This germ-line specific methylation mark was maintained in the preimplantation embryos until the second cleavage stage. Afterwards in the preimplantation embryos, intermediate methylation patterns (26-74% methylation) occurred, which may point to relaxation of the imprints. Intermediate patterns were also present in amniocytes, blood from ICSI babies and adults. We hypothesise that in the early cleavage stage embryo a strict differential methylation pattern is needed for the correct imprint establishment of surrounding imprinted genes. Once correct imprinting of the involved gene(s) is acquired, a more relaxed state of the IG-region is allowed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium-Binding Proteins
  • DNA Methylation*
  • DNA, Intergenic / metabolism*
  • Genomic Imprinting / physiology
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Membrane Proteins / genetics*
  • Proteins / genetics*
  • RNA, Long Noncoding
  • Repetitive Sequences, Nucleic Acid


  • Calcium-Binding Proteins
  • DLK1 protein, human
  • DNA, Intergenic
  • Intercellular Signaling Peptides and Proteins
  • MEG3 non-coding RNA, human
  • Membrane Proteins
  • Proteins
  • RNA, Long Noncoding