Pathway Human Homo sapiens

Maternal to zygotic transition (MZT)

R-HSA-9816359 in Reactome release 97: under Developmental Biology, with 128 genes placed in it by the mapping files and 5 child pathways in the hierarchy.

The same number in the other species

Reactome writes the mouse and rat events it infers from a human pathway under the human number with the species token. A door opens only where that species' own list in this release holds the id; neither of the other two lists holds it. Whether the event was inferred from this one is what the record says.

The record
The genes
Parents and children

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01The record

Reactome's own record of this pathway

What this tells you

The pathway list, the hierarchy and the genes on this page are read from the files Reactome publishes for Reactome release 97, built into this site on 2026-09-09: the pathway list, the hierarchy relationship file and the two gene mapping files. The record card is the one live read, Reactome's own record of this pathway.

Reactome's download page describes the mapping files: Mapping files link the source database identifier to the lowest level pathway diagram or subset of the pathway, all levels of the pathway hierarchy or database identifier to all reactions. [R13] The gene list here is the all-levels mapping of NCBI Gene ids, filled from the all-levels mapping of Ensembl ids where the NCBI file has no row for a gene; each row names which file it came from by the shape of its source id. Each row carries the evidence codes the file writes for it, as written and unranked, and both where the file writes both; no page of Reactome's documentation the survey read defines the codes, so this page does not expand them. A gene id the identity files do not name is kept as the source's own id with no door rather than turned into a symbol.

On citing what a search finds, Reactome says: It should be remembered that while we strive to contain the most current and accurate data, Reactome should not be used in citations where other primary sources of information are available. [R12] The record card prints the literature Reactome attaches to a curated pathway for that reason. The data are public domain: All data in the Reactome database and files derived from that data are licensed under the Creative Commons Public Domain Dedication (CC0). User may copy, modify, and distribute these data, even for commercial purposes, without asking for permission. Attribution is encouraged but not required. [R10] The pathway illustrations are licensed apart, under CC BY 4.0, and none is shown here.

A gene on this list is one Reactome places in this pathway in this release, and that is all the row says: it does not say the gene is expressed in a tissue or associated with a disease, which are the other two explorers' questions, read from other sources. Reactome's papers of record are [R01] [R02].

[R01] Ragueneau E, Gong C, Sinquin P, Sevilla C, Beavers D, Grentner A, et al. (2026). The Reactome Knowledgebase 2026. Nucleic Acids Research 54:D673-D681. PMID 41251150, doi 10.1093/nar/gkaf1223.
[R02] Milacic M, Beavers D, Conley P, Gong C, Gillespie M, Griss J, et al. (2024). The Reactome Pathway Knowledgebase 2024. Nucleic Acids Research 52:D672-D678. PMID 37941124, doi 10.1093/nar/gkad1025.
[R10] Reactome, reactome.org. License Agreement. https://reactome.org/license, read 2026-09-09.
[R12] Reactome, reactome.org. Citing us. https://reactome.org/cite, read 2026-09-09.
[R13] Reactome, reactome.org. Download. https://reactome.org/download-data, read 2026-09-09.

Stable id: R-HSA-9816359.2
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2023-09-13
Events inside: 5, counted from the record

Fertilization of the oocyte triggers the maternal-to-zygotic transition (MZT, reviewed in Vastenhous et al. 2019), a series of events that degrades maternal mRNAs (reviewed in Sha et al. 2019), alters chromatin to allow widespread transcription (reviewed in Eckersley-Maslin et al. 2018), and initiates transcription of the new zygotic genome (zygotic genome activation, ZGA, embryonic genome activation, EGA, reviewed in Wu and Vastenhouw 2020).

Immediately after fertilization, the oocyte completes the final stage of the second meiotic division and the resulting zygote contains separate female and male pronuclei. Within the male pronucleus, protamines are replaced by histones provided by the oocyte (reviewed in McLay and Clarke 2003, Yang et al. 2015). A specific set of maternal mRNAs is degraded by maternally provided factors in a process called M-decay (reviewed in Jiang and Fan 2022) and DNA methylation is lost in both the male pronucleus and the female pronucleus. In mouse zygotes, male DNA methylation is lost in an active process in which cytidine deamination by AICDA (AID) and excision repair initially remove 5-methylcytidine residues, then remaining 5-methylcytidine residues are oxidized by TET3 and removed by base excision repair so that male DNA methylation begins to decrease before fusion of the male and female pronuclei. Maternal DNA methylation is passively lost by dilution over subsequent cell generations, yielding a blastocyst that has low male and female DNA methylation (reviewed in Marcho et al. 2015, Eckersley-Maslin et al. 2018). In human embryos, DNA demethylation in male and female genomes is much faster and is complete by the 2-cell stage, suggesting that maternal DNA demethylation may occur at least partly actively (Guo et al. 2014, reviewed in Tesarik 2022).

In mouse embryos, methylation at histone H3 lysine-4 (H3K4me3), a mark of active chromatin, changes from broad regions that span genes in the maternal genome to peaks at the 5' and 3' ends of genes. Acetylation of H3K27, another mark of active chromatin, increases and methylation of H3K27 and H3K9, repressive marks, becomes reduced (reviewed in Marcho et al. 2015, Eckersley-Maslin et al. 2018). The result is a permissive state of chromatin that produces the first transcription of the zygotic genome and continues into the pluripotent cells of the blastocyst.

Activation of transcription of the zygotic genome, called zygotic genome activation (ZGA) or embryonic genome activation (EGA), occurs in two phases: an initial minor phase followed by a major phase (reviewed in Perry et al. 2022). In mouse zygotes and possibly in human zygotes, the minor phase starts at the 1-cell stage. In mice, the major phase occurs at the 2-cell stage; in humans the major phase occurs at the 8-cell stage. Surprisingly, many transcripts in the early embryo originate from the LTRs of endogenous retroviruses. The LTRs later become silenced after implantation of the embryo.

Developmental pluripotency-associated protein 2 (DPPA2), DPPA4, and Double homeobox protein 4 (DUX4, homolog of mouse Dux) are all key transcription factors that participate in initiating the first, minor wave of ZGA. DPPA2 and DPPA4 activate DUX4 and other genes. DUX4 is actually a small array of identical retroposed genes that were produced by reverse transcription in the germline. DUX4 acting with other factors then activates developmental regulators such as ZSCAN4, the double homeobox genes DUXA, DUXB, LEUTX, and the histone demethylase KDM4E. Significantly, DUX4 binds and activates bidirectional transcription from the LTRs of HERVL endogenous retroviruses and Mammalian Apparent LTRs (MaLRs). Interestingly, human DUX4 and its homolog mouse Dux bind species-specific LTRs, indicating that DUX4 and Dux are coevolving with the endogenous retroviruses in their respective genomes (Whiddon et al. 2017). DUX4 also binds and activates bidirectional transcription of species-specific pericentromeric repeats, the human HSATII repeats.

Activation of the zygotic genome produces factors that further degrade maternal mRNAs in a process called Z-decay (reviewed in Jiang and Fan 2022)

Literature Reactome attaches

A story of birth and death: mRNA translation and clearance at the onset of maternal-to-zygotic transition in mammals†Biol Reprod, 2019, vol. 101, p. 579-590PubMed 30715134
Dynamics of the epigenetic landscape during the maternal-to-zygotic transitionNat Rev Mol Cell Biol, 2018, vol. 19, p. 436-450PubMed 29686419
The maternal-to-zygotic transition revisitedDevelopment, 2019, vol. 146PubMed 31189646
The DNA methylation landscape of human early embryosNature, 2014, vol. 511, p. 606-10PubMed 25079557
Epigenetic dynamics during preimplantation developmentReproduction, 2015, vol. 150, p. R109-20PubMed 26031750
Maternal histone variants and their chaperones promote paternal genome activation and boost somatic cell reprogrammingBioessays, 2015, vol. 37, p. 52-9PubMed 25328107
The initiation of mammalian embryonic transcription: to begin at the beginningTrends Cell Biol, 2022PubMed 36182534

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-10-01 ET · Reactome pathway browser"Maternal to zygotic transition (MZT)". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-9816359 with StableID: R-HSA-9816359.2 (accessed 2026-10-01 ET). Reactome version 97 (CC0).

Reading this pathway's record from Reactome (the pathway record).Still reading. A first read of a pathway can take a while; this page waits up to 35 seconds for it, and its scripts then bring in the panel, or a line saying what did not arrive.

02The genes

Genes Reactome places in this human pathway

The mapping files place 128 genes in this human pathway; showing 101 to 128, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 2 of 2
Gene	Authority id	Mapping file id	Evidence codes
GeneMETTL23	AuthorityHGNC:26988	Mapping file id124512 NCBI file	EvidenceIEA
GeneNOBOX	AuthorityHGNC:22448	Mapping file idENSG00000106410 Ensembl file	EvidenceIEA
GeneNPM2	AuthorityHGNC:7930	Mapping file id10361 NCBI file	EvidenceIEA
GenePABPC1	AuthorityHGNC:8554	Mapping file id26986 NCBI file	EvidenceIEA
GenePABPN1	AuthorityHGNC:8565	Mapping file id8106 NCBI file	EvidenceIEA
GenePABPN1L	AuthorityHGNC:37237	Mapping file id390748 NCBI file	EvidenceIEA
GenePADI6	AuthorityHGNC:20449	Mapping file idENSG00000276747 Ensembl file	EvidenceIEA
GenePAIP1	AuthorityHGNC:16945	Mapping file id10605 NCBI file	EvidenceIEA
GenePAIP2	AuthorityHGNC:17970	Mapping file idENSG00000120727 Ensembl file	EvidenceIEA
GenePOLR2D	AuthorityHGNC:9191	Mapping file idENSG00000144231 Ensembl file	EvidenceIEA
GenePRM1	AuthorityHGNC:9447	Mapping file id5619 NCBI file	EvidenceIEA
GenePRM2	AuthorityHGNC:9448	Mapping file id5620 NCBI file	EvidenceIEA
GeneRPS2	AuthorityHGNC:10404	Mapping file idENSG00000140988 Ensembl file	EvidenceIEA
GeneSRPK1	AuthorityHGNC:11305	Mapping file id6732 NCBI file	EvidenceIEA
GeneSTPG4	AuthorityHGNC:26850	Mapping file id285051 NCBI file	EvidenceIEA
GeneTEAD4	AuthorityHGNC:11717	Mapping file id7004 NCBI file	EvidenceIEA
GeneTET3	AuthorityHGNC:28313	Mapping file id200424 NCBI file	EvidenceIEA
GeneTP53	AuthorityHGNC:11998	Mapping file id7157 NCBI file	EvidenceIEA
GeneTPRX1	AuthorityHGNC:32174	Mapping file id284355 NCBI file	EvidenceIEA, TAS
GeneTPRX2	AuthorityHGNC:32175	Mapping file id503627 NCBI file	EvidenceIEA, TAS
GeneTUT4	AuthorityHGNC:28981	Mapping file id23318 NCBI file	EvidenceIEA
GeneTUT7	AuthorityHGNC:25817	Mapping file id79670 NCBI file	EvidenceIEA
GeneUHRF1	AuthorityHGNC:12556	Mapping file id29128 NCBI file	EvidenceIEA
GeneUNG	AuthorityHGNC:12572	Mapping file id7374 NCBI file	EvidenceIEA
GeneYAP1	AuthorityHGNC:16262	Mapping file id10413 NCBI file	EvidenceIEA
GeneZFP36L2	AuthorityHGNC:1108	Mapping file id678 NCBI file	EvidenceIEA
GeneZP2	AuthorityHGNC:13188	Mapping file idENSG00000103310 Ensembl file	EvidenceIEA
GeneZSCAN4	AuthorityHGNC:23709	Mapping file id201516 NCBI file	EvidenceIEA

Evidence codes on this page: IEA, TAS, as the mapping file writes them; a row carrying two was written twice by the file, once under each. The mapping file id says which file placed the gene: an NCBI Gene id from NCBI2Reactome_All_Levels.txt, an Ensembl gene id from Ensembl2Reactome_All_Levels.txt. The two files can disagree about a code, so a row's codes are the one file's view. Measured by this site's build over this release on 2026-09-09: of the 138,908 human pathway-gene pairs both files place, 207 (0.149 per cent, over 47 genes) carry TAS in the Ensembl file where the NCBI rows carry IEA alone.

Reactome mapping files, the human rows for this pathway · Reactome release 97 · read 2026-09-09 · Reactome downloads"NCBI2Reactome_All_Levels.txt" and "Ensembl2Reactome_All_Levels.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.

03The hierarchy

Parents and children in this release's hierarchy

Parents

Developmental BiologyR-HSA-12667381,589 genes

Children

Reactome's hierarchy is a graph rather than a tree: a pathway can sit under more than one parent, and the gene counts are each pathway's own placements at every level under it, so a parent's count is not the sum of its children's.

Reactome, the human pathway list and hierarchy relationship file · Reactome release 97 · read 2026-09-09 · Reactome downloads"ReactomePathways.txt" and "ReactomePathwaysRelation.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.