Abstract
Parental allele-specific expression of imprinted genes is mediated by
imprinting control regions (ICRs) that are constitutively marked by DNA
methylation imprints on the maternal or paternal allele. Mono-allelic DNA
methylation is strictly required for the process of imprinting and has to be
faithfully maintained during the entire lifespan. While the regulation of DNA
methylation itself is well understood, the mechanisms whereby the opposite
allele remains unmethylated are unclear. Here, we show that in the mouse, at
maternally methylated ICRs, the paternal allele, which is constitutively
associated with H3K4me2/3, is marked by default by H3K27me3 when these ICRs are
transcriptionally inactive, leading to the formation of a bivalent chromatin
signature. Our data suggest that at ICRs, chromatin bivalency has a protective
role by ensuring that DNA on the paternal allele remains unmethylated and
protected against spurious and unscheduled gene expression. Moreover , they
provide the proof of concept that, beside pluripotent cells, chromatin
bivalency is the default state of transcriptionally inactive CpG island
promoters , regardless of the developmental stage, thereby contributing to
protect cell identity.
Citation
ID:
282670
Ref Key:
arnaud2018imprinting