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epigenetic programming in the zygotic pronuclei

Definition

Target type: biologicalprocess

The global programming of epigenetic modifications in the zygote following fertilization. The paternal genome undergoes active DNA demethylation before the first cell division, while the adjacent maternal genome is protected from this process. [GOC:sp, PMID:22868271]

Epigenetic programming in the zygotic pronuclei is a crucial process that establishes the foundation for development by reprogramming the parental genomes. It involves a series of intricate molecular events that re-establish totipotency, erase epigenetic marks inherited from the gametes, and lay the groundwork for lineage specification.

The process commences with the fusion of the sperm and egg, bringing together two haploid genomes. The pronuclei, the male and female nuclei within the fertilized egg, remain separate initially. During this period, active DNA replication occurs, and the parental genomes are prepared for the next crucial phase.

The primary focus of epigenetic programming is the erasure of pre-existing epigenetic marks. These marks, including DNA methylation and histone modifications, are inherited from the parental gametes and reflect their specific cellular identities. The erasure of these marks ensures a clean slate for embryonic development, allowing for totipotency and the potential to generate all cell types.

Several key enzymes and mechanisms are involved in epigenetic reprogramming. Ten-eleven translocation (TET) enzymes catalyze the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), which is an essential step in the demethylation process. Additionally, DNA methyltransferases (DNMTs) play a role in both establishing and erasing DNA methylation patterns.

Simultaneously with DNA methylation reprogramming, histone modifications also undergo substantial changes. Histone acetylation and methylation patterns are dynamically altered, contributing to the establishment of the appropriate chromatin structure and gene expression profile.

Furthermore, a unique class of non-coding RNAs, called piRNAs, play a crucial role in epigenetic programming. PiRNAs protect the integrity of the parental genomes from transposable elements, ensuring their proper silencing.

As the pronuclei migrate towards each other and fuse, the reprogramming process culminates in the formation of the zygotic nucleus. This nucleus now contains the complete diploid genome, which is poised for the first cell division and the initiation of embryogenesis.

The precise timing and sequence of these epigenetic events are tightly regulated, ensuring that the developing embryo acquires the necessary epigenetic landscape for proper development. The disruption of these processes can have profound consequences for embryonic development, leading to developmental abnormalities and disease.'
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Proteins (3)

ProteinDefinitionTaxonomy
Histone-lysine N-methyltransferase SUV39H2A histone-lysine N-methyltransferase SUV39H2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9H5I1]Homo sapiens (human)
DNA damage-binding protein 1A DNA damage-binding protein 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q16531]Homo sapiens (human)
Histone-lysine N-methyltransferase SUV39H1A histone-lysine N-methyltransferase SUV39H1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O43463]Homo sapiens (human)

Compounds (11)

CompoundDefinitionClassesRoles
thalidomide2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione : A dicarboximide that is isoindole-1,3(2H)-dione in which the hydrogen attached to the nitrogen is substituted by a 2,6-dioxopiperidin-3-yl group.

thalidomide : A racemate comprising equimolar amounts of R- and S-thalidomide.

Thalidomide: A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppressive and anti-angiogenic activity. It inhibits release of TUMOR NECROSIS FACTOR-ALPHA from monocytes, and modulates other cytokine action.
phthalimides;
piperidones
gliotoxingliotoxin : A pyrazinoindole with a disulfide bridge spanning a dioxo-substituted pyrazine ring; mycotoxin produced by several species of fungi.

Gliotoxin: A fungal toxin produced by various species of Trichoderma, Gladiocladium fimbriatum, Aspergillus fumigatus, and Penicillium. It is used as an immunosuppressive agent.
dipeptide;
organic disulfide;
organic heterotetracyclic compound;
pyrazinoindole
antifungal agent;
EC 2.5.1.58 (protein farnesyltransferase) inhibitor;
immunosuppressive agent;
mycotoxin;
proteasome inhibitor
pomalidomide3-aminophthalimidoglutarimide: structure in first sourcearomatic amine;
dicarboximide;
isoindoles;
piperidones
angiogenesis inhibitor;
antineoplastic agent;
immunomodulator
lenalidomidearomatic amine;
dicarboximide;
isoindoles;
piperidones
angiogenesis inhibitor;
antineoplastic agent;
immunomodulator
s-adenosylhomocysteineS-adenosyl-L-homocysteine : An organic sulfide that is the S-adenosyl derivative of L-homocysteine.

S-Adenosylhomocysteine: 5'-S-(3-Amino-3-carboxypropyl)-5'-thioadenosine. Formed from S-adenosylmethionine after transmethylation reactions.
adenosines;
amino acid zwitterion;
homocysteine derivative;
homocysteines;
organic sulfide
cofactor;
EC 2.1.1.72 [site-specific DNA-methyltransferase (adenine-specific)] inhibitor;
EC 2.1.1.79 (cyclopropane-fatty-acyl-phospholipid synthase) inhibitor;
epitope;
fundamental metabolite
verticillinsverticillins: 3 antibiotics isolated from imperfect fungus Verticillium: verticillin A, verticillin B (mono-3-hydroxymethyl analog of verticillin A), & verticillin C (differs from verticillin B in that 1 of dioxopiperazine rings has a trisulfide rather than a disulfide bridge; active against gram-positive bacteria & mycobacteria but not against gram-negative bacteria & fungi; RN given refers to cpd with unknown MF; structure (verticillins A & B))
chetomin
jq1 compoundcarboxylic ester;
organochlorine compound;
tert-butyl ester;
thienotriazolodiazepine
angiogenesis inhibitor;
anti-inflammatory agent;
antineoplastic agent;
apoptosis inducer;
bromodomain-containing protein 4 inhibitor;
cardioprotective agent;
ferroptosis inducer
gsk343GSK343 : A member of the class of indazoles that is 1-isopropyl-1H-indazole-4-carboxamide in which the nitrogen of the carboxamide group is substituted by a (6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl group and in which the indazole ring is substituted at position 6 by a 2-(4-methylpiperazin-1-yl)pyridin-4-yl group. A highly potent and selective EZH2 inhibitor (IC50 = 4 nM).

GSK343: an EZH2 methyltransferase inhibitor
aminopyridine;
indazoles;
N-alkylpiperazine;
N-arylpiperazine;
pyridone;
secondary carboxamide
antineoplastic agent;
apoptosis inducer;
EC 2.1.1.43 (enhancer of zeste homolog 2) inhibitor
6,7-dimethoxy-2-(pyrrolidin-1-yl)-n-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine: a SETD8 inhibitor; structure in first source
MZ1organic molecular entity