Postnatal DNA demethylation and its role in tissue maturation
Open accessAbstract
Development in mammals is accompanied by specific de novo and demethylation events that are thought to stabilize differentiated cell phenotypes. We demonstrate that a large percentage of the tissue-specific methylation pattern is generated postnatally. Demethylation in the liver is observed in thousands of enhancer-like sequences associated with genes that undergo activation during the first few weeks of life. Using a conditional gene ablation strategy we show that the removal of these methyl groups is stable and necessary for assuring proper hepatocyte gene expression and function through its effect on chromatin accessibility. These postnatal changes in methylation come about through exposure to hormone signaling. These results define the molecular rules of 5-methyl-cytosine regulation as an epigenetic mechanism underlying cellular responses to a changing environment.
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TET2 and TET3 are known to be required for this 5mC oxidation process in hepatocytes.
“TET2 and TET3 are known to be required for this 5mC oxidation process in hepatocytes (46).”
From Hepatocyte Nuclear Factor 4‐Alpha Is Essential for the Active Epigenetic State at Enhancers in Mouse Liver (2019) · cites this paper as [46]
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- Authors
- Reizel, Y., Sabag, O., Skversky, Y., Spiro, A., Steinberg, B., Bernstein, D., Wang, A., Kieckhaefer, J., Li, C., Pikarsky, E., Levin-Klein, R., Goren, A., Rajewsky, K., Kaestner, K. H., & Cedar, H.
- Affiliations
- Hebrew University of Jerusalem (IL)
- University of Pennsylvania (US)
- Broad Institute (US)
- University of Minnesota (US)
- Max Delbrück Center (DE)
- Corresponding author
- Cedar, Howard
- ORCID
- Venue
- Nature Communications
- Published
- 2018-05-23
- Volume
- 9
- Issue
- 1
- Pages
- 2040-2040
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC5966414
- OpenAlex
- W2804602307
- Cited by
- 83
- References
- 12
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 17 · 2023: 8 · 2022: 10 · 2021: 12 · 2020: 6 · 2019: 11 · 2018: 5
- FWCI
- 3.02
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- Israel Cancer Research Fund
- University of Pennsylvania
- Rosetrees Trust (M31-F2)
- Israel Science Foundation
- National Institutes of Health (1uc4dk104119-01)
- Israeli Centers for Research Excellence
- National Heart, Lung, and Blood Institute (T32HL007062)
- National Institute of General Medical Sciences (T32GM008076)
- National Institute of Diabetes and Digestive and Kidney Diseases (UC4-DK104119, P30DK019525)
- FP7 Ideas: European Research Council (268921, 268614)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- tissue-specific methylation, liver development, hepatocyte gene expression, chromatin accessibility, hormone signaling, epigenetic regulation, 5-methylcytosine, conditional gene deletion, tissue maturation
- MeSH terms
- DNA Demethylation, Animals, Animals, Newborn, Cells, Cultured, DNA-Binding Proteins, Female, Liver, Male, Mice, Inbred C57BL, Proto-Oncogene Proteins, Signal Transduction, Sequence Analysis, RNA, Mice, Knockout, Gene Expression Regulation, Developmental, Hepatocytes, Epigenesis, Genetic, 5-Methylcytosine, Dioxygenases, Mice, High-Throughput Nucleotide Sequencing, Primary Cell Culture
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