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

Area of Science:

• Epigenetics
• Genomic Imprinting
• Molecular Biology

Background:

• Imprinted genes rely on allele-specific differentially methylated regions (DMRs) for regulation.
• CpG methylation in DMRs is established in the germline and maintained in somatic cells.

Purpose of the Study:

• To identify novel epigenetic marks in imprinted gene regulation.
• To investigate the role of these marks in maintaining monoallelic gene expression.

Main Methods:

• Analysis of strand-specific hemimethylation in germline DMRs of murine Peg3 and Snrpn.
• Investigated tetraploid cortical neurons for epigenetic modifications.
• Utilized single nucleotide polymorphism (SNP)-based transcriptional analysis.

Main Results:

• Discovered strand-specific hemimethylation of CpG sites in the Peg3 germline DMR, but not Snrpn.
• Observed enrichment of this hemimethylation in tetraploid cortical neurons.
• Found evidence of formylmethylated CpG sites within the Peg3 DMR.
• Demonstrated that these epigenetic modifications contribute to maintaining Peg3 monoallelic expression.

Conclusions:

• Somatic cells can modify methylation patterns in DMRs, leading to novel epigenetic marks.
• Strand-specific hemimethylated domains are functional in genomic imprinting.
• A new molecular mechanism likely governs the transition from fully methylated to hemimethylated CpGs.