Conserved roles for murine mDUX and human DUX4 in activating cleavage stage genes and MERVL/HERVL retrotransposons [RNA-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 in human pluripotent stem cells (iPSCs). A codon-altered DUX4 (or luciferase control) transgene was cloned into a doxcycline-inducible lentivirus (pCW57.1) and stably integrated. Cells surviving drug-selection were then induced with doxycycline for 14 or 24hrs (two replicates/condition). RNA was collected and 100bp libraries were prepped and sequenced in single-end format.