Zygotic genome activation by the totipotency pioneer factor Nr5a2

Johanna Gassler; Wataru Kobayashi; Imre Gaspar; Siwat Ruangroengkulrith; Adarsh Mohanan; Laura Gomez Hernandez; Pavel Kravchenko; Maximilian Kümmecke; Aleksandar Lalic; Nikita Rifel; Robert Ashburn; Maciej Zaczek; Antoine Vallot; Laura Cuenca Rico; Sabrina Ladstätter; Kikuë Tachibana

doi:10.1126/science.abn7478

Zygotic genome activation by the totipotency pioneer factor Nr5a2

Johanna Gassler, Wataru Kobayashi, Imre Gaspar, Siwat Ruangroengkulrith, Adarsh Mohanan, Laura Gomez Hernandez, Pavel Kravchenko, Maximilian Kümmecke, Aleksandar Lalic, Nikita Rifel, Robert Ashburn, Maciej Zaczek, Antoine Vallot, Laura Cuenca Rico, Sabrina Ladstätter, Kikuë Tachibana (Lead / Corresponding author)

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85 Citations (Scopus)

Abstract

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. On the basis of de novo motif searches, we identified the orphan nuclear receptor Nr5a2 as a key activator of major ZGA in mouse two-cell embryos. Nr5a2 is required for progression beyond the two-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.

Original language	English
Article number	eabn7478
Number of pages	12
Journal	Science
Early online date	24 Nov 2022
DOIs	https://doi.org/10.1126/science.abn7478
Publication status	Published - 23 Dec 2022

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Gassler, J., Kobayashi, W., Gaspar, I., Ruangroengkulrith, S., Mohanan, A., Hernandez, L. G., Kravchenko, P., Kümmecke, M., Lalic, A., Rifel, N., Ashburn, R., Zaczek, M., Vallot, A., Rico, L. C., Ladstätter, S., & Tachibana, K. (2022). Zygotic genome activation by the totipotency pioneer factor Nr5a2. Science, Article eabn7478. https://doi.org/10.1126/science.abn7478

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title = "Zygotic genome activation by the totipotency pioneer factor Nr5a2",

abstract = "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. On the basis of de novo motif searches, we identified the orphan nuclear receptor Nr5a2 as a key activator of major ZGA in mouse two-cell embryos. Nr5a2 is required for progression beyond the two-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.",

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AU - Gassler, Johanna

AU - Kobayashi, Wataru

AU - Gaspar, Imre

AU - Ruangroengkulrith, Siwat

AU - Mohanan, Adarsh

AU - Hernandez, Laura Gomez

AU - Kravchenko, Pavel

AU - Kümmecke, Maximilian

AU - Lalic, Aleksandar

AU - Rifel, Nikita

AU - Ashburn, Robert

AU - Zaczek, Maciej

AU - Vallot, Antoine

AU - Rico, Laura Cuenca

AU - Ladstätter, Sabrina

AU - Tachibana, Kikuë

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AB - 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. On the basis of de novo motif searches, we identified the orphan nuclear receptor Nr5a2 as a key activator of major ZGA in mouse two-cell embryos. Nr5a2 is required for progression beyond the two-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.

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Zygotic genome activation by the totipotency pioneer factor Nr5a2

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