ArticleGenome biology2015
Postnatal epigenetic regulation of intestinal stem cells requires DNA methylation and is guided by the microbiome.
Article in Genome biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 1 of them a synthesis that pooled it.
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Who cites it
95 citing papers in PubMed, 1 synthesis or guideline pooled it, 168 citations in OpenAlex.
- Inflammation and Stem Cell Stochasticity of HPV-induced Cervical Cancer: Epigenetics based Biomarkers through Microbiome and Metabolome for Personalized Medicine: A Systematic Review.Current medicinal chemistry · 2025Pooled it
- Microbial epigenetic regulation as a multilevel regulatory interface in host-microbe interactions.Gut microbes · 2026Review
- The maternal microbiome influence on pregnancy success: breeding comparison of germ-free and conventionalized mice.Gut microbes · 2026Article
- Maternal and infant gut microbiome.iMeta · 2026Review
- Defined bacterial consortium highlights the impact of intestinal bacteria on DNA methylation and tumorigenesis.Genome biology · 2026Article
- Weaning drives microbiome-mediated epigenetic regulation to shape immune memory in mice.Nature microbiology · 2026Article
- Gut microbiota-cholesterol crosstalk in cardiovascular diseases: mechanisms, metabolites, and therapeutic modulation.Nutrition & metabolism · 2025Review
- Gut microbiota and epigenetic inheritance: implications for the development of IBD.Gut microbes · 2025Review
- Multi-strain probiotic administration decreases necrotizing enterocolitis severity and alters the epigenetic profile in mice.Pediatric research · 2025Article
- The molecular basis of lactase persistence: Linking genetics and epigenetics.Annals of human genetics · 2025Review
- Microbiota-driven epigenetic modifications in gastrointestinal cancer: Implications for pathogenesis and therapeutic strategies.World journal of microbiology & biotechnology · 2025Review
- DNA methylation regulates growth traits by influencing metabolic pathways in Pacific white shrimp (Litopenaeus vannamei).BMC genomics · 2025Article
- Epigenetics in evolution and adaptation to environmental challenges: pathways for disease prevention and treatment.Epigenomics · 2025Review
- Review
- Epigenetic modifications of gut microbiota and their potential role in atherosclerosis.Frontiers in pharmacology · 2025Review
- Age-Specific ADME Gene Expression in Infant Intestinal Enteroids.Molecular pharmaceutics · 2024Article
- Gut Microbiota Dysbiosis, Oxidative Stress, Inflammation, and Epigenetic Alterations in Metabolic Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- Dual Regulation Mechanism of Obesity: DNA Methylation and Intestinal Flora.Biomedicines · 2024Review
- Colorectal cancer microbiome programs DNA methylation of host cells by affecting methyl donor metabolism.Genome medicine · 2024Article
- Integrative analysis reveals associations between oral microbiota dysbiosis and host genetic and epigenetic aberrations in oral cavity squamous cell carcinoma.NPJ biofilms and microbiomes · 2024Article
35 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 8 institutions in 1 country.
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Abstract
backgroundDNA methylation is an epigenetic mechanism central to development and maintenance of complex mammalian tissues, but our understanding of its role in intestinal development is limited.
resultsWe use whole genome bisulfite sequencing, and find that differentiation of mouse colonic intestinal stem cells to intestinal epithelium is not associated with major changes in DNA methylation. However, we detect extensive dynamic epigenetic changes in intestinal stem cells and their progeny during the suckling period, suggesting postnatal epigenetic development in this stem cell population. We find that postnatal DNA methylation increases at 3' CpG islands (CGIs) correlate with transcriptional activation of glycosylation genes responsible for intestinal maturation. To directly test whether 3' CGI methylation regulates transcription, we conditionally disrupted two major DNA methyltransferases, Dnmt1 or Dnmt3a, in fetal and adult intestine. Deficiency of Dnmt1 causes severe intestinal abnormalities in neonates and disrupts crypt homeostasis in adults, whereas Dnmt3a loss was compatible with intestinal development. These studies reveal that 3' CGI methylation is functionally involved in the regulation of transcriptional activation in vivo, and that Dnmt1 is a critical regulator of postnatal epigenetic changes in intestinal stem cells. Finally, we show that postnatal 3' CGI methylation and associated gene activation in intestinal epithelial cells are significantly altered by germ-free conditions.
conclusionsOur results demonstrate that the suckling period is critical for epigenetic development of intestinal stem cells, with potential important implications for lifelong gut health, and that the gut microbiome guides and/or facilitates these postnatal epigenetic processes.
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