TBP regulates transposable element expression in early mouse embryos

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 highly expressed 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. Surprisingly, we find the general transcription factor TBP directly and specifically activates MaLRs. Loss-of-function of TBP in mouse embryos 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. We demonstrate that TBP regulates MaLRs through direct binding. Our work contributes to the identification of regulators of TE expression in vivo and highlights a previously unrecognised role for a general transcription factor in regulating an exquisitely specific TE transcriptional programme. Overall design: Late 2-cell stage embryos were collected and Cut&Tag was performed using TBP antibody and IGG as control.