Visualizing Changes in Cdkn1c Expression Links Early-Life Adversity to Imprint Mis-regulation in Adults
Open accessAbstract
Imprinted genes are regulated according to parental origin and can influence embryonic growth and metabolism and confer disease susceptibility. Here, we designed sensitive allele-specific reporters to non-invasively monitor imprinted Cdkn1c expression in mice and showed that expression was modulated by environmental factors encountered in utero. Acute exposure to chromatin-modifying drugs resulted in de-repression of paternally inherited (silent) Cdkn1c alleles in embryos that was temporary and resolved after birth. In contrast, deprivation of maternal dietary protein in utero provoked permanent de-repression of imprinted Cdkn1c expression that was sustained into adulthood and occurred through a folate-dependent mechanism of DNA methylation loss. Given the function of imprinted genes in regulating behavior and metabolic processes in adults, these results establish imprinting deregulation as a credible mechanism linking early-life adversity to later-life outcomes. Furthermore, Cdkn1c-luciferase mice offer non-invasive tools to identify factors that disrupt epigenetic processes and strategies to limit their long-term impact.
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Inserting a fluorescent protein gene reporter into a methylation-sensitive locus provides a direct readout of methylation status in living cells or a whole animal.
“In an alternative strategy, the fluorescent protein gene reporter can be directly inserted into the methylation sensitive locus which provides a direct readout of the methylation status in living cells or a whole animal (54).”
From Dynamic DNA methylation: In the right place at the right time (2018) · cites this paper as [54]
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References 43 · Cited by 55
- Authors
- Van de Pette, M., Abbas, A., Feytout, A., McNamara, G., Bruno, L., To, W. K., Dimond, A., Sardini, A., Webster, Z., McGinty, J., Paul, E. J., Ungless, M. A., French, P. M. W., Withers, D. J., Uren, A., Ferguson-Smith, A. C., Merkenschlager, M., John, R. M., & Fisher, A. G.
- Affiliations
- Hammersmith Hospital (GB)
- Imperial College London (GB)
- Cardiff University (GB)
- Corresponding author
- Fisher, Amanda G.
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2017-01
- Volume
- 18
- Issue
- 5
- Pages
- 1090-1099
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC5300902
- OpenAlex
- W2585390996
- Cited by
- 55
- References
- 43
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 9 · 2023: 9 · 2022: 4 · 2021: 5 · 2020: 5 · 2019: 7 · 2018: 7 · 2017: 2
- FWCI
- 3.77
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion, other-oa)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo (cc-by)
- Funders
- Medical Research Council
- Biotechnology and Biological Sciences Research Council (BB/J015156)
- National Institute for Health and Care Research
- European Research Council (294627)
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Keywords
- genomic imprinting, CDKN1C, childhood adversity, DNA methylation, epigenetic inheritance
- MeSH terms
- Alleles, Animals, Chromatin, Genomic Imprinting, DNA Methylation, Epigenesis, Genetic, Cyclin-Dependent Kinase Inhibitor p57, Mice
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