DUX4 regulates oocyte to embryo transition in human

Sanna Vuoristo; Christel Hydén‐Granskog; Masahito Yoshihara; Shruti Bhagat; Lisa M. Gawriyski; Eeva‐Mari Jouhilahti; Anastassius Damdimopoulos; Vipin Ranga; Mahlet Z. Tamirat; Mikko T Huhtala; Kosuke Hashimoto; Kaarel Krjutškov; Gaëlle Recher; Sini Ezer; Priit Paluoja; Pauliina Paloviita; Yujiro Takegami; Ai Kanemaru; Karolina Lundin; Tomi T. Airenne; Timo Otonkoski; Juha S. Tapanainen; Hideya Kawaji; Yasuhiro Murakawa; Thomas R. Bürglin; Markku T Varjosalo; Mark S. Johnson; Timo Tuuri; Shintaro Katayama; Juha Kere

doi:10.1101/732289

Developmental BiologybioRxivFeb 13, 2020

Preprint

DUX4 regulates oocyte to embryo transition in human

Sanna Vuoristo iD, Christel Hydén‐Granskog iD, Masahito Yoshihara iD, Shruti Bhagat iD, Lisa M. Gawriyski iD, Eeva‐Mari Jouhilahti iD, Anastassius Damdimopoulos, Vipin Ranga iD, Mahlet Z. Tamirat iD, Mikko T Huhtala iD, Kosuke Hashimoto iD, Kaarel Krjutškov iD, Gaëlle Recher iD, Sini Ezer iD, Priit Paluoja iD, Pauliina Paloviita iD, Yujiro Takegami, Ai Kanemaru, Karolina Lundin iD, Tomi T. Airenne iD, Timo Otonkoski iD, Juha S. Tapanainen iD, Hideya Kawaji iD, Yasuhiro Murakawa iD, Thomas R. Bürglin iD, , Juha Kere iD

Abstract

During the human oocyte-to-embryo transition, the fertilized oocyte undergoes final maturation and the embryo genome is gradually activated during the first three cell divisions. How this transition is coordinated in humans is largely unknown. We show that the double homeodomain transcription factor DUX4 contributes to this transition. DUX4 knockdown in human zygotes caused insufficient transcriptome reprogramming as observed three days after fertilization. Induced DUX4 expression in human embryonic stem cells activated transcription of thousands of newly identified bi-directional transcripts, including putative enhancers for embryonic genome activation genes such as LEUTX. DUX4 protein interacted with transcriptional modifiers that are known to couple enhancers and promoters. Taken together, our results reveal that DUX4 is a pioneer regulating oocyte-to-embryo transition in human through activation of intergenic genome, especially enhancers, and hence setting the stage for early human embryo development.

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