TBP regulates transposable element expression in early mouse embryos

The activation of the embryonic genome is a crucial step in development. In addition to thousands of genes, many transposable elements (TEs) are robustly transcribed during early mammalian development. However, their transcriptional regulators remain largely unexplored. Here, we set out to identify transcription factors regulating the expression of TEs from the LINE, SINE and ERVL families during mouse preimplantation development. In particular, the MaLR family are the most abundant ERVL in the mouse genome and are also the most abundant constituent of the transcriptome in early mouse embryos. We find that the general transcription factor TBP binds and activates MaLRs in mouse embryos. Loss-of-function of TBP leads to downregulation of MaLRs, specifically the ORR1A family, which is the youngest ORR subclass and contributes a significant portion of major zygotic genome activation transcripts. Our work identifies regulators of TE expression in vivo and highlights a previously unrecognised role for the general transcription factor TBP in regulating a highly specific TE transcriptional programme.