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

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 We ectopically overexpressed human DUX4 (or luciferase control) in human pluripotent stem cells (iPSCs) by dox -induction for 18hrs. Cells were then lysed and chromatin was immunoprecipitated using a rabbit monoclonal anti-DUX4 antibody [E5-5] (ab124699) . 125bp libraries were prepped (2 technical replicates/condition) and sequenced in paired-end format. All sequencing was done on the Illumina HiSeq 2500 platform.