Pathway
Replacement of protamines by nucleosomes in the male pronucleus
In human sperm, about 85 to 90% of the genome is associated with protamines rather than histones (reviewed in Torres-Flores and Hernández-Hernández 2020, Ribas-Maynou et al. 2022). Protamines provide a much higher packing density of DNA in the nucleus but there are few reports of epigenetic marks on protamines. After fertilization, protamines in the male pronucleus are replaced with histones provided by the oocyte cytoplasm (reviewed in Yang et al. 2015, Okada and Yamaguchi 2017). The result is a decondensation of sperm chromatin that produces a chromatin state that is permissive for transcription.
Continue reading
Dissociation of protamines from DNA appears to be controlled by phosphorylation of the protamines PRM1 and PRM2 (inferred from mouse homologs in Gou et al. 2020). The kinase SRPK1 phosphorylates both PRM1 and PRM2, which recruit the histone chaperones Nucleoplasmin 2 (NPM2) and HIRA (inferred from mouse homologs in Gou et al. 2020). NPM2 then dissociates the phosphorylated PRM1 from DNA. By inference NPM1 and NPM3, which are also present in the zygote, may also dissociate PRM1 and PRM2 from DNA.
Nucleosomes in the zygote are characterized by H3.3 and H2AX (H2A.X) (reviewed in Martire and Banaszynski 2020). HIRA chaperones histone H3.3 and acts together with NPM proteins to assemble nucleosomes from individual histone proteins. Asymmetric dimethylation of H3.3 arginine-17 catalyzed by METTL23 is required for assembly of H3.3 into chromatin in the male pronucleus (inferred from mouse homologs in Hatanaka et al. 2017). The oocyte-specific histone H1, H1FOO (H1.8, H1-8), is also deposited on the newly formed chromatin at this time and persists until the 8-cell stage. In mouse embryos, H1foo is not required for development.
What the reference databases state
Statements
22 statements
22 statements · 1 reference database · Subject: Replacement of protamines by nucleosomes in the male pronucleus · Sources: Reactome
- H1-8 participates in Replacement of protamines by nucleosomes in the male pronucleusProteinReactome R-HSA-9821993Inferred only
- H2AX participates in Replacement of protamines by nucleosomes in the male pronucleusProteinReactome R-HSA-9821993Inferred only
- H2BC1 participates in Replacement of protamines by nucleosomes in the male pronucleusProteinReactome R-HSA-9821993Inferred only
- H2BC11 participates in Replacement of protamines by nucleosomes in the male pronucleusProteinReactome R-HSA-9821993Inferred only
- H2BC12 participates in Replacement of protamines by nucleosomes in the male pronucleusProteinReactome R-HSA-9821993Inferred only
- H2BC13 participates in Replacement of protamines by nucleosomes in the male pronucleusProteinReactome R-HSA-9821993Inferred only
- H2BC14 participates in Replacement of protamines by nucleosomes in the male pronucleusProteinReactome R-HSA-9821993Inferred only
- H2BC15 participates in Replacement of protamines by nucleosomes in the male pronucleusProteinReactome R-HSA-9821993Inferred only
- H2BC17 participates in Replacement of protamines by nucleosomes in the male pronucleusProteinReactome R-HSA-9821993Inferred only
- H2BC21 participates in Replacement of protamines by nucleosomes in the male pronucleusProteinReactome R-HSA-9821993Inferred only
- H2BC26 participates in Replacement of protamines by nucleosomes in the male pronucleusProteinReactome R-HSA-9821993Inferred only
- H2BC3 participates in Replacement of protamines by nucleosomes in the male pronucleusProteinReactome R-HSA-9821993Inferred only
Show the remaining 10
- H2BC4; H2BC6; H2BC7; H2BC8; H2BC10 participates in Replacement of protamines by nucleosomes in the male pronucleusProteinReactome R-HSA-9821993Inferred only
- H2BC9 participates in Replacement of protamines by nucleosomes in the male pronucleusProteinReactome R-HSA-9821993Inferred only
- H3-3A; H3-3B participates in Replacement of protamines by nucleosomes in the male pronucleusProteinReactome R-HSA-9821993Inferred only
- H4C1; H4C2; H4C3; H4C4; H4C5; H4C6; H4C8; H4C9; H4C11; H4C12; H4C13; H4C14; H4C15; H4C16 participates in Replacement of protamines by nucleosomes in the male pronucleusProteinReactome R-HSA-9821993Inferred only
- HIRA participates in Replacement of protamines by nucleosomes in the male pronucleusProteinReactome R-HSA-9821993Inferred only
- METTL23 participates in Replacement of protamines by nucleosomes in the male pronucleusProteinReactome R-HSA-9821993Inferred only
- NPM2 participates in Replacement of protamines by nucleosomes in the male pronucleusProteinReactome R-HSA-9821993Inferred only
- PRM1 participates in Replacement of protamines by nucleosomes in the male pronucleusProteinReactome R-HSA-9821993Inferred only
- PRM2 participates in Replacement of protamines by nucleosomes in the male pronucleusProteinReactome R-HSA-9821993Inferred only
- SRPK1 participates in Replacement of protamines by nucleosomes in the male pronucleusProteinReactome R-HSA-9821993Inferred only