Transgenerational epigenetic inheritance in mammals remains a debated subject. Here, we demonstrate that DNA methylation of promoter-associated CpG islands (CGIs) can be transmitted from parents to their offspring in mice. We generated DNA methylation-edited mouse embryonic stem cells (ESCs), in which CGIs of two metabolism-related genes, the Ankyrin repeat domain 26 and the low-density lipoprotein receptor, were specifically methylated and silenced. DNA methylation-edited mice generated by microinjection of the methylated ESCs exhibited abnormal metabolic phenotypes. Acquired methylation of the targeted CGI and the phenotypic traits were maintained and transmitted across multiple generations. The heritable CGI methylation was subjected to reprogramming in parental PGCs and subsequently reestablished in the next generation at post-implantation stages. These observations provide a concrete step toward demonstrating transgenerational epigenetic inheritance in mammals, which may have implications in our understanding of evolutionary biology as well as the etiology, diagnosis, and prevention of non-genetically inherited human diseases.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.cell.2022.12.047 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
CpG hypomethylation at proximal promoter and 5'UTR along with IL6 signaling loop associates with MYD88 upregulation in epithelial ovarian cancer.
Sci Rep
December 2024
Department Gynecological Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, No. 55, Section 4, South People's Road, Chengdu, 610041, China.
MYD88 is an IL-6 primary response gene and, its upregulation of expression has been shown to be a poor prognostic factor in epithelial ovarian cancer (EOC). We investigated the effects of CpG methylation at the proximal promoter/5'UTR and IL-6/SP1/IRF1 signaling on upregulation of MYD88 and prognosis in EOC. We assessed CpG methylation at the proximal promoter/5'UTR of MYD88 using bisulfite sequencing/PCR in 103 EOC patients, 28 normal ovarian tissues and two EOC cell lines with differential expression of MYD88 and identified the impact of the level of CpG methylation on MYD88 upregulation by SP1/IRF1 with knockdown or blockade of IL-6.
View Article and Find Full Text PDFAttenuated sex-related DNA methylation differences in cancer highlight the magnitude bias mediating existing disparities.
Biol Sex Differ
December 2024
State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China.
Background: DNA methylation (DNAm) influences both sex differences and cancer development, yet the mechanisms connecting these factors remain unclear.
Methods: Utilizing data from The Cancer Genome Atlas, we conducted a comprehensive analysis of sex-related DNAm effects in nine non-reproductive cancers, compared to paired normal adjacent tissues (NATs), and validated the results using independent datasets. First, we assessed the extent of sex differential DNAm between cancers and NATs to explore how sex-related DNAm differences change in cancerous tissues.
Epigenetic Regulation of Nuclear Factor Erythroid-2-Related Factor 2 in Colorectal Cancer Cells Resistant to Ionizing Radiation.
Biomol Ther (Seoul)
January 2025
Department of Biochemistry, College of Medicine, and Jeju Natural Medicine Research Center, Jeju National University, Jeju 63243, Republic of Korea.
γ-Radiation resistance is a major obstacle to the success of radiotherapy in colorectal cancer. Antioxidant-related factors contribute to resistance to radiation therapy and, therefore, are targets for improving the therapeutic response. In this study, we evaluated the molecular mechanisms underlying γ-radiation resistance using the colorectal cancer cell line SNUC5 and γ-radiation-resistant variant SNUC5/RR, including analyses of the role of nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor that regulates antioxidant enzymes, and related epigenetic regulators.
View Article and Find Full Text PDF[DNA Methylation Profiling in Aneurysm and Comorbid Atherosclerosis of the Ascending Aorta].
Mol Biol (Mosk)
December 2024
Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, 634050 Russia.
Atherosclerosis and aneurysm of the aorta are relatively common pathological conditions that remain asymptomatic for a long period of time and have life-threatening and disabling complications. DNA methylation profiling in several regions (a dilated area, a nondilated area, and an atherosclerotic plaque) of the ascending aorta was carried out in patients with aortic aneurysm. DNA methylation was analyzed by reduced representation bisulfite sequencing (RRBS).
View Article and Find Full Text PDFImpact of excess sugar on the whole genome DNA methylation pattern in human sperm.
Epigenomics
December 2024
Epigenetics and Diabetes Unit, Department of Clinical Sciences in Malmö, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, Sweden.
Aims, Patients & Methods: Dietary factors may regulate the epigenome. We aimed to explore whether a diet intervention, including excess sugar, affects the methylome in human sperm, and to describe the sperm methylome. We used Whole Genome Bisulfite Sequencing (WGBS) to analyze DNA methylation in sperm taken at three time points from 15 males during a diet intervention; i) at baseline, ii) after one week on a standardized diet, and iii) after an additional week on a high-sugar diet providing 150% of their estimated total energy expenditure.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!