Tet enzymes are essential for embryogenesis and completion of embryonic genome activation

Mammalian embryo development begins in transcriptional silence followed by activation of thousands of genes. Reprogramming of DNA methylation is integral to embryogenesis and linked to Tet enzymes; however, their function in early development is not fully understood. Here, we generated combined deficiencies of all three Tet enzymes in mouse oocytes and observed arrest at 2-cell stage with the most severe phenotype linked to Tet2. Gene expression analysis revealed that Tet enzymes are required for completion of embryonic genome activation. Our results demonstrate that Tet enzymes have non-redundant roles and are key components of EGA in mammalian embryos. Overall design: RNA-Seq of control-morpholino injected, Tet3-morpholino injected, Tet1-, Tet2-, and Tet3-morpholino injected 2-cell embryos (11 replicates each) as well as alpha-amanitin treated 2-cell embryos (12 replicates) and negative controls (3 replicates)