Expression of DUX4 in the zygote

Stable Identifier
R-HSA-9816369
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
nucleoplasm
ReviewStatus
5/5
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Expression of DUX4 in the zygote
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DUX4 is expressed in human zygotes (Vuoristo et al. 2022) and cleavage stage embryos (Hendrickson et al. 2017). DUX4 mRNA appears in the zygote then decreases in 2-cell and 4-cell embryos: DUX4 protein increases during the 2-cell to 4-cell stages and decreases by the 8-cell stage (Vuoristo et al. 2022). DUX4 protein becomes nuclearly localized in 2-cell embryos and remains in the nucleus in 4-cell embryos. Nuclear localization of DUX4 precedes and coincides with the initial, minor phase of zygotic genome activation (ZGA) and DUX4 activates many ZGA genes such as ZSCAN4, DUXA, and LEUTX (Vuoristo et al. 2022). Promoters and enhancer-like regions activated by DUX4 are enriched for MaLR-ERVL endogenous retrovirus sequences (Vuoristo et al. 2022). By inference from mouse homologs, DPPA2 and DPPA4 directly activate DUX4 expression in the zygote. Activated TP53 (p53) also binds near the DUX4 gene and activates expression (Grow et al. 2021).
Literature References
PubMed ID Title Journal Year
35402882 DUX4 is a multifunctional factor priming human embryonic genome activation

Vuoristo, S, Bhagat, S, Hydén-Granskog, C, Yoshihara, M, Gawriyski, L, Jouhilahti, EM, Ranga, V, Tamirat, M, Huhtala, M, Kirjanov, I, Nykänen, S, Krjutškov, K, Damdimopoulos, A, Weltner, J, Hashimoto, K, Recher, G, Ezer, S, Paluoja, P, Paloviita, P, Takegami, Y, Kanemaru, A, Lundin, K, Airenne, TT, Otonkoski, T, Tapanainen, JS, Kawaji, H, Murakawa, Y, Bürglin, TR, Varjosalo, M, Johnson, MS, Tuuri, T, Katayama, S, Kere, J

iScience 2022
28459457 Conserved roles of mouse DUX and human DUX4 in activating cleavage-stage genes and MERVL/HERVL retrotransposons

Hendrickson, PG, Doráis, JA, Grow, EJ, Whiddon, JL, Lim, JW, Wike, CL, Weaver, BD, Pflueger, C, Emery, BR, Wilcox, AL, Nix, DA, Peterson, CM, Tapscott, SJ, Carrell, DT, Cairns, BR

Nat Genet 2017
34267371 p53 convergently activates Dux/DUX4 in embryonic stem cells and in facioscapulohumeral muscular dystrophy cell models

Grow, EJ, Weaver, BD, Smith, CM, Guo, J, Stein, P, Shadle, SC, Hendrickson, PG, Johnson, NE, Butterfield, RJ, Menafra, R, Kloet, SL, van der Maarel, SM, Williams, CJ, Cairns, BR

Nat Genet 2021
Participants
Input
Output
Participates
as an event of
This event is regulated
Positively by
Regulator
DPPA2:DPPA4:p-S15-TP53:DUX4 gene [nucleoplasm] (Homo sapiens)
Inferred From
Expression of Dux in the embryo (Mus musculus)
Authored
May, B  (2022-09-07)
Reviewed
Xie, W  (2023-08-08)
Created
May, B  (2022-09-12)
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