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Zygotic genome activation (ZGA)

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-9819196

PubChem

R-HSA-9819196

Description

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).

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SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

Displaying **all 6** entries
UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
P04637	Cellular tumor antigen p53	P53 TP53	view
P46937	Transcriptional coactivator YAP1	YAP1 YAP65	view
Q09472	Histone acetyltransferase p300	EP300 P300	view
Q15561	Transcriptional enhancer factor TEF-3	RTEF1 TCF13L1 TEAD4 TEF3	view
Q5TAX3	Terminal uridylyltransferase 4	KIAA0191 TUT4 ZCCHC11	view
Q92793	CREB-binding protein	CBP CREBBP	view

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