Strand-specific CpG hemimethylation, a novel epigenetic modification functional for genomic imprinting

• Published in: Nucleic acids research Vol. 45; no. 15; pp. 8822 - 8834
• Main Authors: Patiño-Parrado, Iris, Gómez-Jiménez, Álvaro, López-Sánchez, Noelia, Frade, José M
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 06.09.2017
• Subjects: 5-Methylcytosine - metabolism; Alleles; Animals; Base Sequence; Cell Nucleus - genetics; Cell Nucleus - metabolism; Cerebral Cortex - cytology; Cerebral Cortex - metabolism; CpG Islands; DNA Methylation; Embryo, Mammalian; Epigenesis, Genetic; Gene regulation, Chromatin and Epigenetics; Genomic Imprinting; Kruppel-Like Transcription Factors - genetics; Kruppel-Like Transcription Factors - metabolism; Male; Mice; Mice, Inbred C57BL; Neurons - cytology; Neurons - metabolism; Polymorphism, Single Nucleotide; Sequence Alignment; Tetraploidy; Transcription, Genetic
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gkx518

Imprinted genes are regulated by allele-specific differentially DNA-methylated regions (DMRs). Epigenetic methylation of the CpGs constituting these DMRs is established in the germline, resulting in a 5-methylcytosine-specific pattern that is tightly maintained in somatic tissues. Here, we show a novel epigenetic mark, characterized by strand-specific hemimethylation of contiguous CpG sites affecting the germline DMR of the murine Peg3, but not Snrpn, imprinted domain. This modification is enriched in tetraploid cortical neurons, a cell type where evidence for a small proportion of formylmethylated CpG sites within the Peg3-controlling DMR is also provided. Single nucleotide polymorphism (SNP)-based transcriptional analysis indicated that these epigenetic modifications participate in the maintainance of the monoallelic expression pattern of the Peg3 imprinted gene. Our results unexpectedly demonstrate that the methylation pattern observed in DMRs controlling defined imprinting regions can be modified in somatic cells, resulting in a novel epigenetic modification that gives rise to strand-specific hemimethylated domains functional for genomic imprinting. We anticipate the existence of a novel molecular mechanism regulating the transition from fully methylated CpGs to strand-specific hemimethylated CpGs.