Zygotic genome activation (ZGA)

Stable Identifier
R-HSA-9819196
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
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Zygotic genome activation (ZGA)
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After fertilization the maternal and paternal pronuclei undergo major changes in epigenetic modifications, including demethylation of DNA and changes in methylation and acetylation of histones. At this 1-cell stage in mouse zygotes and possibly in human zygotes (Asami et al. 2022), a minor wave of expression from both the female and male genomes occurs, the minor zygotic genome activation (ZGA, also known as embryonic genome activation, EGA) (reviewed in Eckersley-Maslin et al. 2018, Schulz and Harrison 2019, Wu and Vastenhouw 2020, Aoki 2022).
Among the first loci to be transcribed is the DUX4 array of double-homeobox transcription factors. (DUX4 appears to be homologous in structure and function with Dux of mice.) DUX4 binds the promoters of ZGA-expressed genes such as ZSCAN4, DUXA, DUXB, LEUTX, and KDM4E and interacts with the Mediator complex to activate transcription (Vuoristo et al. 2022, reviewed in Kobayashi and Tachibana 2021).
DUX4 also binds long terminal repeats (LTRs) of thousands of endogenous retroelements, notably the HERVL family of retroelements, and activates bidirectional transcription that can initiate expression of adjacent genes (reviewed in Fu et al. 2019, Low et al. 2021). Interestingly, this transcription of endogenous retroviruses evidently results in production of retrovirus-like particles in the plasma and tissues of human embryos (Mondal and Hofschneider 1982).
DUX4 binds HSATII pericentric satellite repeats (Young et al. 2013, Hendrickson et al. 2017) and initiates bidirectional transcription (Hendrickson et al. 2017, Shadle et al. 2019). The transcripts appear to be required for subsequent formation of chromocenters, large multichromosome conglomerations of heterochromatin (Probst et al. 2010).
The minor ZGA is followed by the major ZGA at the 2-cell stage in mice and the 8-cell stage in humans. During the major ZGA, chromatin reverts to a more usual configuration, with broad regions of histone H3 trimethyllysine-4 across genes converted to narrow peaks near transcription start sites (reviewed in Eckersley-Maslin et al. 2018, Schulz and Harrison 2019, Wu and Vastenhouw 2020, Aoki 2022). Histones H3.1 and H3.2 are also added at this time (Ishiuchi et al. 2021).
Literature References
PubMed ID Title Journal Year
34256217 Awakening of the zygotic genome by pioneer transcription factors

Tachibana, K, Kobayashi, W

Curr Opin Struct Biol 2021
7129678 Isolation and characterization of retrovirus-like elements from normal human fetuses

Mondal, H, Hofschneider, PH

Int J Cancer 1982
24278031 DUX4 binding to retroelements creates promoters that are active in FSHD muscle and testis

Balog, J, Snider, L, Tawil, R, Whiddon, JL, van der Maarel, SM, Geng, LN, Tapscott, SJ, Young, JM, Kasinathan, B, Yao, Z

PLoS Genet 2013
30759824 Endogenous Retroviruses Function as Gene Expression Regulatory Elements During Mammalian Pre-implantation Embryo Development

Fu, B, Liu, D, Ma, H

Int J Mol Sci 2019
35402882 DUX4 is a multifunctional factor priming human embryonic genome activation

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

iScience 2022
32591075 From mother to embryo: A molecular perspective on zygotic genome activation

Wu, E, Vastenhouw, NL

Curr Top Dev Biol 2020
34691189 Transposable Element Dynamics and Regulation during Zygotic Genome Activation in Mammalian Embryos and Embryonic Stem Cell Model Systems

Hu, Z, Tee, WW, Tan, DEK, Low, Y, Tan, SYX

Stem Cells Int 2021
31630170 DUX4-induced bidirectional HSATII satellite repeat transcripts form intranuclear double-stranded RNA foci in human cell models of FSHD

Shadle, SC, Bass, BL, van der Maarel, SM, Wong, CJ, Karreman, NA, Tapscott, SJ, Bennett, SR, Campbell, AE

Hum Mol Genet 2019
35034936 Zygotic gene activation in mice: profile and regulation

Aoki, F

J Reprod Dev 2022
20951352 A strand-specific burst in transcription of pericentric satellites is required for chromocenter formation and early mouse development

Le Baccon, P, Probst, AV, Okamoto, I, Casanova, M, Almouzni, G, El Marjou, F

Dev Cell 2010
29686419 Dynamics of the epigenetic landscape during the maternal-to-zygotic transition

Reik, W, Alda-Catalinas, C, Eckersley-Maslin, MA

Nat Rev Mol Cell Biol 2018
33169018 Reprogramming of the histone H3.3 landscape in the early mouse embryo

Abe, S, Yeung, WKA, Miki, Y, Sasaki, H, Ishiuchi, T, Ogura, A, Inoue, K

Nat Struct Mol Biol 2021
28459457 Conserved roles of mouse DUX and human DUX4 in activating cleavage-stage genes and MERVL/HERVL retrotransposons

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

Nat Genet 2017
30573849 Mechanisms regulating zygotic genome activation

Harrison, MM, Schulz, KN

Nat Rev Genet 2019
34936886 Human embryonic genome activation initiates at the one-cell stage

Asami, M, VerMilyea, MD, Rainbow, K, Lam, BYH, Braun, S, Ma, MK, Perry, ACF, Yeo, GSH

Cell Stem Cell 2022
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Go Biological Process
maternal-to-zygotic transition of gene expression (0160021)
Authored
May, B  (2022-10-30)
Reviewed
Xie, W  (2023-08-08)
Created
May, B  (2022-11-02)
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