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Udgivet

Mother-child transmission of epigenetic information by tunable polymorphic imprinting

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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  • Brittany L Carpenter
  • Wanding Zhou
  • Zachary Madaj
  • Ashley K DeWitt
  • Jason P Ross
  • Kirsten Grønbæk
  • Gangning Liang
  • Susan J Clark
  • Peter L Molloy
  • Peter A Jones
Vis graf over relationer

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.

OriginalsprogEngelsk
TidsskriftProceedings of the National Academy of Sciences of the United States of America
Vol/bind115
Udgave nummer51
Sider (fra-til)E11970-E11977
Antal sider8
ISSN0027-8424
DOI
StatusUdgivet - 18 dec. 2018

ID: 56422660