Search results for DPPA4

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Protein (1 results from a total of 1)

Identifier: R-HSA-452999
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: DPPA4: Q7L190

DNA Sequence (1 results from a total of 1)

Identifier: R-HSA-6800123
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: ENSEMBL: ENSEMBL:ENSG00000121570

Reaction (4 results from a total of 4)

Identifier: R-HSA-452701
Species: Homo sapiens
Compartment: nucleoplasm
DPPA4 is expressed in pluripotent stem cells. The promoter of the DPPA4 gene binds OCT4 (POU5F1), SOX2, and NANOG (Player et al. 2006, Boyer et al. 2007, inferred from mouse homologs in Chakravarthy et al. 2008). OCT4 Knockdown experiments show OCT4 enhances expression of DPPA4 (Babaie et al. 2007).
Identifier: R-HSA-6800120
Species: Homo sapiens
Compartment: nucleoplasm
POU5F1, SOX2, and NANOG bind the promoter of the DPPA4 gene and activate transcription of DPPA4 (Player et al. 2006, Boyer et al. 2007).
Identifier: R-HSA-9816389
Species: Homo sapiens
Compartment: nucleoplasm
Activated TP53 (phosphoSer15-TP53) binds a LTR10C repeat about 18 kb from the DUX4 locus between DUX4 and the telomere of chromosome 4q (Grow et al. 2021). DPPA2 and DPPA4 also bind the promoter of the DUX4 gene (inferred from mouse homologs). DUX4 is an intronless and presumably retroposed gene located in a 3.3 kb macrosatellite that is present as 11-150 repeats in the D4Z4 region of chromosome 4 (Hewitt et al. 1994).
Identifier: R-HSA-9816369
Species: Homo sapiens
Compartment: nucleoplasm
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).

Complex (1 results from a total of 1)

Identifier: R-HSA-9816394
Species: Homo sapiens
Compartment: nucleoplasm

Pathway (1 results from a total of 1)

Identifier: R-HSA-9816359
Species: Homo sapiens
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)

Icon (1 results from a total of 1)

Species: Homo sapiens
Curator: Bruce May
Designer: Cristoffer Sevilla
DPPA4 icon
Developmental pluripotency-associated protein 4.
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