Tet enzymes are essential for early embryogenesis and completion of embryonic genome activation
Year: 2021
Type: article
Abstract: Mammalian development begins in transcriptional silence followed by a period of widespread activation of thousands of genes. DNA methylation reprogramming is integral to embryogenesis and linked to Tet enzymes, but their function in early development is not well understood. Here, we generate combined deficiencies of all three Tet enzymes in mouse oocytes using a morpholino-guided knockdown approach and study the impact of acute Tet enzyme deficiencies on preimplantation development. Tet1-3 deficient embryos arrest at the 2-cell stage with the most severe phenotype linked to Tet2. Individual Tet enzymes display non-redundant roles in the consecutive oxidation of 5-methylcytosine to 5-carboxylcytosine. Gene expression analysis uncovers that Tet enzymes are required for completion of embryonic genome activation (EGA) and fine-tuned expression of transposable elements and chimeric transcripts. Whole-genome bisulfite sequencing reveals minor changes of global DNA methylation in Tet-deficient 2-cell embryos, suggesting an important role of non-catalytic functions of Tet enzymes in early embryogenesis. Our results demonstrate that Tet enzymes are key components of the clock that regulates the timing and extent of EGA in mammalian embryos.
Source: EMBO Reports
Authors: Julia Arand, H Rosaria Chiang, David Martin, Michael P Snyder, Julien Sage, Renee A Reijo Pera, Mark Wossidlo
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,200
Funders: Siebel Stem Cell Institute, Deutsche Forschungsgemeinschaft, National Institutes of Health, School of Medicine, Stanford University, National Heart, Lung, and Blood Institute, National Cancer Institute, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Stanford Maternal and Child Health Research Institute
OpenAlex ID: W4200469338