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 1 to 100, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 1 of 2
Gene	Authority id	Mapping file id	Evidence codes
GeneAGO2	AuthorityHGNC:3263	Mapping file id27161 NCBI file	EvidenceIEA
GeneAICDA	AuthorityHGNC:13203	Mapping file id57379 NCBI file	EvidenceIEA
GeneBTG4	AuthorityHGNC:13862	Mapping file id54766 NCBI file	EvidenceIEA
GeneCNOT1	AuthorityHGNC:7877	Mapping file id23019 NCBI file	EvidenceIEA
GeneCNOT10	AuthorityHGNC:23817	Mapping file id25904 NCBI file	EvidenceIEA
GeneCNOT11	AuthorityHGNC:25217	Mapping file id55571 NCBI file	EvidenceIEA
GeneCNOT12	AuthorityHGNC:19081	Mapping file id85456 NCBI file	EvidenceIEA
GeneCNOT2	AuthorityHGNC:7878	Mapping file id4848 NCBI file	EvidenceIEA
GeneCNOT3	AuthorityHGNC:7879	Mapping file id4849 NCBI file	EvidenceIEA
GeneCNOT4	AuthorityHGNC:7880	Mapping file id4850 NCBI file	EvidenceIEA
GeneCNOT6	AuthorityHGNC:14099	Mapping file id57472 NCBI file	EvidenceIEA
GeneCNOT6L	AuthorityHGNC:18042	Mapping file id246175 NCBI file	EvidenceIEA
GeneCNOT7	AuthorityHGNC:14101	Mapping file id29883 NCBI file	EvidenceIEA
GeneCNOT8	AuthorityHGNC:9207	Mapping file id9337 NCBI file	EvidenceIEA
GeneCNOT9	AuthorityHGNC:10445	Mapping file id9125 NCBI file	EvidenceIEA
GeneCREBBP	AuthorityHGNC:2348	Mapping file id1387 NCBI file	EvidenceIEA
GeneDICER1	AuthorityHGNC:17098	Mapping file id23405 NCBI file	EvidenceIEA
GeneDIS3L2	AuthorityHGNC:28648	Mapping file id129563 NCBI file	EvidenceIEA
GeneDPPA2	AuthorityHGNC:19197	Mapping file id151871 NCBI file	EvidenceIEA
GeneDPPA3	AuthorityHGNC:19199	Mapping file id359787 NCBI file	EvidenceIEA
GeneDPPA4	AuthorityHGNC:19200	Mapping file id55211 NCBI file	EvidenceIEA
GeneDUX4	AuthorityHGNC:50800	Mapping file id100288687 NCBI file	EvidenceIEA, TAS
GeneDUXA	AuthorityHGNC:32179	Mapping file id503835 NCBI file	EvidenceTAS
GeneDUXB	AuthorityHGNC:33345	Mapping file id100033411 NCBI file	EvidenceTAS
GeneEIF4A1	AuthorityHGNC:3282	Mapping file id1973 NCBI file	EvidenceIEA
GeneEIF4A2	AuthorityHGNC:3284	Mapping file id1974 NCBI file	EvidenceIEA
GeneEIF4A3	AuthorityHGNC:18683	Mapping file id9775 NCBI file	EvidenceIEA
GeneEIF4B	AuthorityHGNC:3285	Mapping file id1975 NCBI file	EvidenceIEA
GeneEIF4E	AuthorityHGNC:3287	Mapping file id1977 NCBI file	EvidenceIEA
GeneEIF4G1	AuthorityHGNC:3296	Mapping file id1981 NCBI file	EvidenceIEA
GeneELOC	AuthorityHGNC:11617	Mapping file idENSG00000154582 Ensembl file	EvidenceIEA
GeneEP300	AuthorityHGNC:3373	Mapping file id2033 NCBI file	EvidenceIEA
GeneFGF8	AuthorityHGNC:3686	Mapping file idENSG00000107831 Ensembl file	EvidenceIEA
GeneH1-8	AuthorityHGNC:18463	Mapping file id132243 NCBI file	EvidenceIEA
GeneH2AB1	AuthorityHGNC:22516	Mapping file id474382 NCBI file	EvidenceIEA
GeneH2AC14	AuthorityHGNC:4727	Mapping file id8331 NCBI file	EvidenceIEA
GeneH2AC18	AuthorityHGNC:4736	Mapping file id8337 NCBI file	EvidenceIEA
GeneH2AC19	AuthorityHGNC:29668	Mapping file id723790 NCBI file	EvidenceIEA
GeneH2AC20	AuthorityHGNC:4738	Mapping file id8338 NCBI file	EvidenceIEA
GeneH2AC4	AuthorityHGNC:4734	Mapping file id8335 NCBI file	EvidenceIEA
GeneH2AC6	AuthorityHGNC:4733	Mapping file id8334 NCBI file	EvidenceIEA
GeneH2AC7	AuthorityHGNC:4729	Mapping file id3013 NCBI file	EvidenceIEA
GeneH2AC8	AuthorityHGNC:4724	Mapping file id3012 NCBI file	EvidenceIEA
GeneH2AJ	AuthorityHGNC:14456	Mapping file id55766 NCBI file	EvidenceIEA
GeneH2AX	AuthorityHGNC:4739	Mapping file id3014 NCBI file	EvidenceIEA
GeneH2AZ2	AuthorityHGNC:20664	Mapping file id94239 NCBI file	EvidenceIEA
GeneH2BC1	AuthorityHGNC:18730	Mapping file id255626 NCBI file	EvidenceIEA
GeneH2BC10	AuthorityHGNC:4756	Mapping file id8346 NCBI file	EvidenceIEA
GeneH2BC11	AuthorityHGNC:4761	Mapping file id8970 NCBI file	EvidenceIEA
GeneH2BC12	AuthorityHGNC:13954	Mapping file id85236 NCBI file	EvidenceIEA
GeneH2BC12L	AuthorityHGNC:4762	Mapping file id54145 NCBI file	EvidenceIEA
GeneH2BC13	AuthorityHGNC:4748	Mapping file id8340 NCBI file	EvidenceIEA
GeneH2BC14	AuthorityHGNC:4750	Mapping file id8342 NCBI file	EvidenceIEA
GeneH2BC15	AuthorityHGNC:4749	Mapping file id8341 NCBI file	EvidenceIEA
GeneH2BC17	AuthorityHGNC:4758	Mapping file id8348 NCBI file	EvidenceIEA
GeneH2BC21	AuthorityHGNC:4760	Mapping file id8349 NCBI file	EvidenceIEA
GeneH2BC26	AuthorityHGNC:20514	Mapping file id128312 NCBI file	EvidenceIEA
GeneH2BC3	AuthorityHGNC:4751	Mapping file id3018 NCBI file	EvidenceIEA
GeneH2BC4	AuthorityHGNC:4757	Mapping file id8347 NCBI file	EvidenceIEA
GeneH2BC5	AuthorityHGNC:4747	Mapping file id3017 NCBI file	EvidenceIEA
GeneH2BC6	AuthorityHGNC:4753	Mapping file id8344 NCBI file	EvidenceIEA
GeneH2BC7	AuthorityHGNC:4752	Mapping file id8343 NCBI file	EvidenceIEA
GeneH2BC8	AuthorityHGNC:4746	Mapping file id8339 NCBI file	EvidenceIEA
GeneH2BC9	AuthorityHGNC:4755	Mapping file id8345 NCBI file	EvidenceIEA
GeneH3-3A	AuthorityHGNC:4764	Mapping file id3020 NCBI file	EvidenceIEA
GeneH3-3B	AuthorityHGNC:4765	Mapping file id3021 NCBI file	EvidenceIEA
GeneH3C1	AuthorityHGNC:4766	Mapping file id8350 NCBI file	EvidenceIEA
GeneH3C10	AuthorityHGNC:4775	Mapping file id8357 NCBI file	EvidenceIEA
GeneH3C11	AuthorityHGNC:4771	Mapping file id8354 NCBI file	EvidenceIEA
GeneH3C12	AuthorityHGNC:4774	Mapping file id8356 NCBI file	EvidenceIEA
GeneH3C13	AuthorityHGNC:25311	Mapping file id653604 NCBI file	EvidenceIEA
GeneH3C14	AuthorityHGNC:20503	Mapping file id126961 NCBI file	EvidenceIEA
GeneH3C15	AuthorityHGNC:20505	Mapping file id333932 NCBI file	EvidenceIEA
GeneH3C2	AuthorityHGNC:4776	Mapping file id8358 NCBI file	EvidenceIEA
GeneH3C3	AuthorityHGNC:4768	Mapping file id8352 NCBI file	EvidenceIEA
GeneH3C4	AuthorityHGNC:4767	Mapping file id8351 NCBI file	EvidenceIEA
GeneH3C6	AuthorityHGNC:4769	Mapping file id8353 NCBI file	EvidenceIEA
GeneH3C7	AuthorityHGNC:4773	Mapping file id8968 NCBI file	EvidenceIEA
GeneH3C8	AuthorityHGNC:4772	Mapping file id8355 NCBI file	EvidenceIEA
GeneH4C1	AuthorityHGNC:4781	Mapping file id8359 NCBI file	EvidenceIEA
GeneH4C11	AuthorityHGNC:4785	Mapping file id8363 NCBI file	EvidenceIEA
GeneH4C12	AuthorityHGNC:4784	Mapping file id8362 NCBI file	EvidenceIEA
GeneH4C13	AuthorityHGNC:4791	Mapping file id8368 NCBI file	EvidenceIEA
GeneH4C14	AuthorityHGNC:4794	Mapping file id8370 NCBI file	EvidenceIEA
GeneH4C15	AuthorityHGNC:29607	Mapping file id554313 NCBI file	EvidenceIEA
GeneH4C16	AuthorityHGNC:20510	Mapping file id121504 NCBI file	EvidenceIEA
GeneH4C2	AuthorityHGNC:4789	Mapping file id8366 NCBI file	EvidenceIEA
GeneH4C3	AuthorityHGNC:4787	Mapping file id8364 NCBI file	EvidenceIEA
GeneH4C4	AuthorityHGNC:4782	Mapping file id8360 NCBI file	EvidenceIEA
GeneH4C5	AuthorityHGNC:4790	Mapping file id8367 NCBI file	EvidenceIEA
GeneH4C6	AuthorityHGNC:4783	Mapping file id8361 NCBI file	EvidenceIEA
GeneH4C8	AuthorityHGNC:4788	Mapping file id8365 NCBI file	EvidenceIEA
GeneH4C9	AuthorityHGNC:4793	Mapping file id8294 NCBI file	EvidenceIEA
GeneHIRA	AuthorityHGNC:4916	Mapping file id7290 NCBI file	EvidenceIEA
GeneKDM4E	AuthorityHGNC:37098	Mapping file id390245 NCBI file	EvidenceTAS
GeneKDM5A	AuthorityHGNC:9886	Mapping file id5927 NCBI file	EvidenceIEA
GeneKDM5B	AuthorityHGNC:18039	Mapping file id10765 NCBI file	EvidenceIEA
GeneKDM6A	AuthorityHGNC:12637	Mapping file id7403 NCBI file	EvidenceIEA
GeneKDM6B	AuthorityHGNC:29012	Mapping file id23135 NCBI file	EvidenceIEA
GeneLEUTX	AuthorityHGNC:31953	Mapping file id342900 NCBI file	EvidenceTAS

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.