DUX4 is a multifunctional factor priming human embryonic genome activation

Sanna Vuoristo, Shruti Bhagat, Christel Hydén-Granskog, Masahito Yoshihara, Lisa Gawriyski, Eeva-Mari Jouhilahti, Vipin Ranga, Mahlet Tamirat, Mikko Huhtala, Ida Kirjanov, Sonja Nykänen, Kaarel Krjutškov, Anastassius Damdimopoulos, Jere Weltner, Kosuke Hashimoto, Gaëlle Recher, Sini Ezer, Priit Paluoja, Pauliina Paloviita, Yujiro TakegamiAi Kanemaru, Karolina Lundin, Tomi T Airenne, Timo Otonkoski, Juha S Tapanainen, Hideya Kawaji, Yasuhiro Murakawa, Thomas R Bürglin, Markku Varjosalo, Mark S Johnson, Timo Tuuri, Shintaro Katayama, Juha Kere

Tutkimustuotos: LehtiartikkeliArtikkeliTieteellinenvertaisarvioitu

2 Sitaatiot (Scopus)

Abstrakti

Double homeobox 4 (DUX4) is expressed at the early pre-implantation stage in human embryos. Here we show that induced human DUX4 expression 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) genes ZSCAN4 and KHDC1P1. We show that DUX4 is markedly enriched in human zygotes, followed by intense nuclear DUX4 localization preceding and coinciding with minor EGA. DUX4 knockdown 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 of DUX4 as a regulator of the non-coding genome.

AlkuperäiskieliEnglanti
Artikkeli104137
Sivumäärä29
JulkaisuiScience
Vuosikerta25
Numero4
DOI - pysyväislinkit
TilaJulkaistu - 15 huhtik. 2022
OKM-julkaisutyyppiA1 Julkaistu artikkeli, soviteltu

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