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

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 derived and analyzed transcriptomes from seven stages of developing human oocytes and embryos. The blastocyst stage embryos were dissected into inner cell mass (ICM) and trophectoderm lineages and processed independently. Cells from each stage were pooled and RNA was extracted. Two stranded libraries were prepared from each stage. Each library was then split and amplied for 12 or 14 PCR cycles, resulting in four technical replicates per developmental stage. 12 and14 cycle replicates from the same library prep were merged after sequencing

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Hendrickson PG, Doráis JA, Grow EJ, Whiddon JL, Lim JW, Wike CL, Weaver BD, Pflueger C, Emery BR, Wilcox AL, Nix DA, Peterson CM, Tapscott SJ, Carrell DT, Cairns BR