Methylation pattern of polymorphically imprinted nc886 is not conserved across mammalia

Area of Science:

• Genetics and Epigenetics
• Developmental Biology
• Comparative Genomics

Background:

• The nc886 locus in humans is a polymorphically imprinted metastable epiallele.
• Periconceptional conditions influence nc886 methylation, linked to later-life health outcomes per the Developmental Origins of Health and Disease (DOHaD) hypothesis.
• Animal models could elucidate associations between periconceptional factors, nc886 methylation, and metabolic phenotypes.

Purpose of the Study:

• To investigate the DNA methylation pattern of the nc886 locus in various non-human mammals.
• To determine the applicability of non-human models for studying nc886 methylation and its implications for DOHaD.

Main Methods:

• Acquired DNA methylation data from the GEO repository for mammals with high sequence similarity to human nc886.
• Included data from humans, great apes (chimpanzees, bonobos, gorillas, orangutans), Old World monkeys (baboons, macaques, vervets), marmosets, and guinea pigs.
• Analyzed nc886 methylation patterns and compared them with sequence data of flanking CTCF binding sites.

Main Results:

• Human nc886 data showed a bimodal distribution, confirming polymorphic imprinting.
• Great apes exhibited a unimodal pattern (50% methylation), Old World monkeys showed higher variation (approx. 60% methylation), and guinea pigs had a non-methylated region.
• Sequence analysis of CTCF binding sites supported the observed DNA methylation patterns across species.

Conclusions:

• The nc886 locus is not a polymorphically imprinted metastable epiallele in non-human primates or guinea pigs.
• These findings indicate that animal models are not suitable for nc886 research.
• The nc886 region appears classically imprinted in great apes and potentially Old World monkeys, but not in guinea pigs.