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Proc Natl Acad Sci U S A. 2018 Dec 18;115(51):E11970-E11977. doi: 10.1073/pnas.1815005115. Epub 2018 Dec 3.

Mother-child transmission of epigenetic information by tunable polymorphic imprinting.

Author information

1
Center for Epigenetics, Van Andel Research Institute, Grand Rapids, MI 49503.
2
Nutrition and Health Program, CSIRO Health and Biosecurity, North Ryde, NSW 2113, Australia.
3
Department of Hematology, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark.
4
Biotech Research and Innovation Centre (BRIC), Faculty of Health Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.
5
Department of Urology, University of Southern California, Los Angeles, CA 90089.
6
Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089.
7
Genomics and Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.
8
Center for Epigenetics, Van Andel Research Institute, Grand Rapids, MI 49503; peter.jones@vai.org.

Abstract

Genomic imprinting mediated by DNA methylation restricts gene expression to a single allele determined by parental origin and is not generally considered to be under genetic or environmental influence. Here, we focused on a differentially methylated region (DMR) of approximately 1.9 kb that includes a 101-bp noncoding RNA gene (nc886/VTRNA2-1), which is maternally imprinted in ∼75% of humans. This is unlike other imprinted genes, which demonstrate monoallelic methylation in 100% of individuals. The DMR includes a CTCF binding site on the centromeric side defining the DMR boundary and is flanked by a CTCF binding site on the telomeric side. The centromeric CTCF binding site contains an A/C polymorphism (rs2346018); the C allele is associated with less imprinting. The frequency of imprinting of the nc886 DMR in infants was linked to at least two nongenetic factors, maternal age at delivery and season of conception. In a separate cohort, nc886 imprinting was associated with lower body mass index in children at 5 y of age. Thus, we propose that the imprinting status of the nc886 DMR is "tunable" in that it is associated with maternal haplotype and prenatal environment. This provides a potential mechanism for transmitting information, with phenotypic consequences, from mother to child.

KEYWORDS:

DNA methylation; VTRNA2-1; epigenetic inheritance; nc886; polymorphic imprinting

Conflict of interest statement

Conflict of interest statement: P.A.J. is a paid consultant for Zymo Research. In this study, Zymo Research reagents were used to analyze locus-specific DNA methylation patterns.

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