Zygotic genome activation by the totipotency pioneer factor Nr5a2
Johanna Gassler, Wataru Kobayashi, Imre Gáspár, Siwat Ruangroengkulrith, Adarsh Mohanan, Laura Gómez Hernández, Pavel Kravchenko, Maximilian Kümmecke, Aleksandar Lalic, Nikita Rifel, Robert John Ashburn, Maciej Zaczek, Antoine Vallot, Laura Cuenca Rico, Sabrina Ladstätter, and Kikuë Tachibana (24 Nov 2022) Zygotic genome activation by the totipotency pioneer factor Nr5a2. Science 378 (6626) 1305-1315. DOI: 10.1126/science.abn7478
Abstract cited from the article:
Life begins with a switch in genetic control from the maternal to the embryonic genome during zygotic genome activation (ZGA). Despite its importance, the essential regulators of ZGA remain largely unknown in mammals. Based on de novo motif searches, we identified the orphan nuclear receptor Nr5a2 as a key activator of major ZGA in mouse 2-cell embryos. Nr5a2 is required for progression beyond the 2-cell stage. It binds to its motif within SINE B1/Alu retrotransposable elements found in cis-regulatory regions of ZGA genes. Chemical inhibition suggests that 72% of ZGA genes are regulated by Nr5a2 and potentially other orphan nuclear receptors. Nr5a2 promotes chromatin accessibility during ZGA and binds nucleosomal DNA in vitro. We conclude that Nr5a2 is an essential pioneer factor that regulates ZGA.