How maternal factors in oocytes trigger zygotic genome activation (ZGA) is a long-standing question in developmental biology.  Recent studies in 2-cell like embryonic stem cells (2C-like cells) implicate that the DUX family transcription factors are key regulators of ZGA in placental mammals.  To characterize the role of DUX in ZGA, we generated Dux cluster knockout (KO) mouse lines. Unexpectedly, we found both Dux zygotic KO (Z-KO) and maternal/zygotic KO (MZ-KO) embryos can survive to adulthood despite showing reduced developmental potential.  Furthermore, transcriptome profiling of the MZ-KO embryos revealed that loss of DUX has minimal effect on ZGA and most DUX targets in 2C-like cells are normally activated in MZ-KO embryos.  Thus, contrary to the key function in inducing 2C-like cells, our data indicate that DUX only has a minor role in ZGA and loss of DUX is compatible with mouse development. SOURCE: Zhiyuan Chen (Zhiyuan.Chen@childrens.harvard.edu) -  Harvard Medical School/Boston Children's Hospital

Pluto Bioinformatics

GSE121746: Loss of DUX causes minor defects in zygotic genome activation and is compatible with mouse development