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2017 ; 45
(15
): 8822-8834
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Strand-specific CpG hemimethylation, a novel epigenetic modification functional
for genomic imprinting
#MMPMID28605464
Patiño-Parrado I
; Gómez-Jiménez Á
; López-Sánchez N
; Frade JM
Nucleic Acids Res
2017[Sep]; 45
(15
): 8822-8834
PMID28605464
show ga
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.