Parental epigenomes are established during gametogenesis. While they are largely reset after fertilization, broad domains of Polycomb repressive complex 2 (PRC2)-mediated formation of lysine 27-trimethylated histone H3 (H3K27me3) are inherited from oocytes in mice. How maternal H3K27me3 is established and inherited by embryos remains elusive. Here, we show that PRC1-mediated formation of lysine 119-monoubiquititinated histone H2A (H2AK119ub1) confers maternally heritable H3K27me3. Temporal profiling of H2AK119ub1 dynamics revealed that atypically broad H2AK119ub1 domains are established, along with H3K27me3, during oocyte growth. From the two-cell stage, H2AK119ub1 is progressively deposited at typical Polycomb targets and precedes H3K27me3. Reduction of H2AK119ub1 by depletion of Polycomb group ring finger 1 (PCGF1) and PCGF6-essential components of variant PRC1 (vPRC1)-leads to H3K27me3 loss at a subset of genes in oocytes. The gene-selective H3K27me3 deficiency is irreversibly inherited by embryos, causing loss of maternal H3K27me3-dependent imprinting, embryonic sublethality and placental enlargement at term. Collectively, our study unveils preceding dynamics of H2AK119ub1 over H3K27me3 at the maternal-to-zygotic transition, and identifies PCGF1/6-vPRC1 as an essential player in maternal epigenetic inheritance.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/s41588-021-00820-3 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Isolation of proteins on chromatin (iPOC) reveals signaling pathway-dependent alterations in the DNA-bound proteome.
Mol Cell Proteomics
January 2025
Division of Proteomics of Stem Cell and Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg Germany; Medical Faculty, Heidelberg University, 69120 Heidelberg, Germany. Electronic address:
Signaling pathways often convergence on transcription factors (TFs) and other DNA-binding proteins (DBPs) that regulate chromatin structure and gene expression, thereby governing a broad range of essential cellular functions. However, the repertoire of DBPs is incompletely understood even for the best-characterized pathways. Here, we optimized a strategy for the isolation of Proteins on Chromatin (iPOC) exploiting tagged nucleoside analogues to label the DNA and capture associated proteins, thus enabling the comprehensive, sensitive, and unbiased characterization of the DNA-bound proteome.
View Article and Find Full Text PDFKDM6B-dependent epigenetic programming of uterine fibroblasts in early pregnancy regulates parturition timing in mice.
Cell
January 2025
Biomedical Sciences Program, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Bakar ImmunoX Initiative, University of California, San Francisco, San Francisco, CA 94143, USA; Center for Reproductive Science, School of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address:
Current efforts investigating parturition timing mechanisms have focused on the proximal triggers of labor onset generated in late pregnancy. By studying the delayed parturition phenotype of mice with uterine fibroblast deficiencies in the histone H3K27me3 demethylase KDM6B, we provide evidence that parturition timing is regulated by events that take place in early pregnancy. Immediately after copulation, uterine fibroblasts engage in a locus-specific epigenetic program that abruptly adjusts H3K27me3 levels across their genome.
View Article and Find Full Text PDFIntroduction: This study designed to examine whether social/ environmental experiences can induce the epigenetic modification, and influence the associated physiology and behaviour. To test this, we have used social stress [prenatal stress (PNS)] model and then housed at environmental enrichment (EE) condition to evaluate the interaction between specific epigenetic modification and its influence on behaviour.
Methods: Pregnant rats were randomly divided into a control group, PNS group, and PNS+EE group.
Marek's disease virus-encoded microRNA-M6-5p facilitates viral latent infection by targeting histone demethylase KDM2B.
J Virol
January 2025
Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, Beijing, China.
Marek's disease virus (MDV), a highly contagious and oncogenic avian alphaherpesvirus, establishes a latent infection primarily in CD4 T cells. Latent infections are necessary for both persistent lifelong MDV infection and viral tumorigenesis. MicroRNAs (miRNAs) play critical roles as post-transcriptional regulators of viral infections.
View Article and Find Full Text PDFMineral Stress Drives Loss of Heterochromatin: An Early Harbinger of Vascular Inflammaging and Calcification.
Circ Res
January 2025
British Heart Foundation Centre for Research Excellence, School of Cardiovascular and Metabolic Medicine and Sciences, James Black Centre, King's College London, United Kingdom (C.Y.H., M.-Y.W., J.T., S.A., L.D., G.A., R.H., C.M.S.).
Background: Vascular calcification is a detrimental aging pathology markedly accelerated in patients with chronic kidney disease. Prelamin A is a biomarker of vascular smooth muscle cell aging that accelerates calcification however the mechanisms remain undefined.
Methods: Vascular smooth muscle cells were transduced with prelamin A using an adenoviral vector and epigenetic modifications were monitored using immunofluorescence and targeted polymerase chain reaction array.
Want 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!