Conserved roles for murine mDUX and human DUX4 in activating cleavage stage genes and MERVL/HERVL retrotransposons [ChIP-Seq Mouse]. Mus musculus

To better understand transcriptional regulation during human oogenesis and pre-implantation embryonic development, we defined stage-specific transcription, which revealed cleavage stage as highly distinctive. We present multiple lines of evidence that two cleavage-specific homologs, mouse mDUX and human DUX4, each activate hundreds of cleavage-specific endogenous genes (e.g. ZSCAN4, ZFP352, KDM4E) and retroviral elements (MERVL/HERVL-family). Remarkably, mDux expression converts mouse ESCs into two-cell embryo-like (2C-like) cells by binding to MERVL promoters/enhancers and restoring the chromatin landscape (via ATACseq) to the pattern of mouse two-cell embryos Overall design: We ectopically overexpressed and HA-tagged mouse DUX (mDux) in mESCs by treating stable cells (TRE::3xHA-mDux; MERVL::EGFP) with doxycycline for 24hrs. Cells were then lysed to extract chromatin for immunoprecipitation. 125bp libraries were prepped and sequenced in paired-end format. All sequencing was done on the Illumina HiSeq 2500 platform.