title: Methylation analysis of the intergenic differentially methylated region of DLK1-GTL2 in human.
abstract: 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.
authors.affiliation: Research Centre Reproduction and Genetics, University Hospital and Medical School of the Vrije Universiteit Brussel, Laarbeeklaan, Brussels, Belgium.
authors.forename: Elke
authors.initials: E
authors.lastname: Geuns
authors.forename: Nele
authors.initials: N
authors.lastname: De Temmerman
authors.forename: Pierre
authors.initials: P
authors.lastname: Hilven
authors.forename: André
authors.initials: A
authors.lastname: Van Steirteghem
authors.forename: Inge
authors.initials: I
authors.lastname: Liebaers
authors.forename: Martine
authors.initials: M
authors.lastname: De Rycke
mesh_terms: D002135:Calcium-Binding Proteins; D019175:DNA Methylation; D021901:DNA, Intergenic / Q000378:metabolism*; D018392:Genomic Imprinting / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D062085:RNA, Long Noncoding; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D021901:DNA, Intergenic; D036341:Intercellular Signaling Peptides and Proteins; C498907:MEG3 non-coding RNA, human; D008565:Membrane Proteins; D011506:Proteins; D062085:RNA, Long Noncoding