摘要：SummaryDouble homeobox 4 (DUX4) is expressed at the early pre-implantation stage in human embryos. Here we show that induced humanDUX4expression substantially alters the chromatin accessibility of non-coding DNA and activates thousands of newly identified transcribed enhancer-like regions, preferentially located within ERVL-MaLR repeat elements. CRISPR activation of transcribed enhancers by C-terminal DUX4 motifs results in the increased expression of target embryonic genome activation (EGA) genesZSCAN4andKHDC1P1. We show thatDUX4is markedly enriched in human zygotes, followed by intense nuclear DUX4 localization preceding and coinciding with minor EGA.DUX4knockdown in human zygotes led to changes in the EGA transcriptome but did not terminate the embryos. We also show that the DUX4 protein interacts with the Mediator complex via the C-terminal KIX binding motif. Our findings contribute to the understanding ofDUX4as a regulator of the non-coding genome.Graphical abstractDisplay OmittedHighlights•DUX4 induces the expression of thousands of accessible, transcribed putative enhancers•DUX4RNA is enriched in human zygotes; the protein is enriched in the nucleus before EGA•DUX4knockdown in human zygotes leads to minor embryonic transcriptome changes•DUX4 protein interacts with the Mediator complex via the KIX binding motifDevelopmental biology; Biology of human development; Molecular biology
