While tuning into signals is the name of the game for (epi)genomics, an exciting new study now suggests that genetic and environmental factors can tune our epigenomes by polymorphic genomic imprinting. Unlike other imprinted genes that always display monoallelic methylation, the nc886 DMR is polymorphic and imprinted in only ~75% of people. New research into this unique case by the lab of Peter Jones (Van Andel Research Institute, Michigan) has uncovered that genetic variation in a CTCF binding site and prenatal environmental factors both exert an associative influence on an imprinted DMR with physiological relevance.
The imprinted locus of interest comprises a ~1.9 kb differentially methylated region (DMR) that contains the 101 bp noncoding RNA nc886 (VTRNA2-1). While the monoallelic methylation of the nc886 DMR has been previously investigated by the group and others before, a re-examination of previous 450k array epigenome-wide association studies (EWAS) uncovered some surprising insights into imprinting biology.
Here’s what the team discovered about the nc886 DMR:
- nc886 displays maternal methylation when imprinting occurs, as it is not methylated in sperm
- Genetic variation plays a role in this polymorphic imprinting
- The C allele of an A/C SNP in a methylation sensitive CTCF site associates with less imprinting
- The environment also influences polymorphic imprinting, as evidenced by the examination of two separate studies of maternal age and maternal nutrition at conception
- In a cohort of 114 children from Gambia, the authors uncovered imprinting of nc886 in 93% of children conceived during the rainy season, when nutritious food was plentiful; however, only 73% of children exposed to a food shortage during an unusually dry growing season exhibited imprinting
- In another cohort, they found imprinting in 47% of babies born to mothers under 20, and 75% imprinting in babies born to mothers over twenty
- By re-examining another study, the team discovered that a lower body mass index at age 5 associates with nc886 imprinting
Together, these associative results highlight a potential scenario where genetic and environmental factors can combine to shape the establishment of an imprinted DMR that affects human physiology.