Target type: biologicalprocess
The global programming of epigenetic modifications in the female pronucleus of the newly fertilized zygote. The maternal genome is protected from global DNA demethylation before the first division of the zygote, and instead undergoes passive, replication-dependent demethylation during early embryogenesis, arising from inhibition of the DNA maintenance methyltransferase Dnmt1. [GOC:sp, PMID:22868271]
Epigenetic programming of the female pronucleus is a complex and crucial process that establishes the initial epigenetic landscape of the developing embryo. This process involves the erasure and re-establishment of epigenetic marks, primarily DNA methylation and histone modifications, which play a vital role in regulating gene expression.
The female pronucleus, derived from the oocyte, carries the maternal genome. Upon fertilization, the female pronucleus undergoes a series of epigenetic changes to ensure proper development.
1. **Global Demethylation:** The oocyte possesses a specific methylation pattern, characterized by high levels of DNA methylation. Upon fertilization, the female pronucleus undergoes active demethylation, removing these pre-existing methylation marks. This process is mediated by ten-eleven translocation (TET) enzymes, which convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), a key intermediate in the demethylation pathway.
2. **Re-Establishment of De Novo Methylation:** As demethylation proceeds, new methylation patterns are established, reflecting the developmental stage and the specific cell lineage. This de novo methylation is carried out by DNA methyltransferases (DNMTs), primarily DNMT3A and DNMT3B. These enzymes establish methylation patterns that are crucial for silencing repetitive elements and ensuring appropriate gene expression.
3. **Histone Modifications:** Along with DNA methylation, histone modifications, such as acetylation, methylation, and phosphorylation, play a crucial role in regulating gene expression. These modifications are influenced by various enzymes, including histone acetyltransferases (HATs), histone deacetylases (HDACs), histone methyltransferases (HMTs), and histone demethylases (HDMs). They orchestrate changes in chromatin structure, impacting accessibility to DNA and influencing gene transcription.
4. **Imprinting:** A unique aspect of epigenetic programming is the establishment of genomic imprinting. This process involves differential methylation of specific genomic regions based on parental origin. Imprinted genes are expressed exclusively from either the maternal or paternal allele, contributing to proper embryonic development.
5. **X-Chromosome Inactivation:** In female embryos, one of the two X chromosomes is inactivated to equalize gene expression between males and females. This process, known as X-chromosome inactivation (XCI), involves the silencing of one X chromosome through epigenetic modifications, including methylation and histone modifications.
The epigenetic programming of the female pronucleus is a tightly regulated and complex process that establishes the initial epigenetic landscape of the embryo. Any disruptions in this process can lead to developmental defects and diseases. This intricate interplay of epigenetic modifications is essential for proper embryonic development, ensuring the correct temporal and spatial expression of genes needed for the formation of a healthy organism.'
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Protein | Definition | Taxonomy |
---|---|---|
DNA (cytosine-5)-methyltransferase 3-like | A DNA (cytosine-5)-methyltransferase 3-like that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9UJW3] | Homo sapiens (human) |
Lysine-specific histone demethylase 1B | A lysine-specific histone demethylase 2 that is encoded in the genome of human. [PRO:HJD, UniProtKB:Q8NB78] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
procainamide | procainamide : A benzamide that is 4-aminobenzamide substituted on the amide N by a 2-(diethylamino)ethyl group. It is a pharmaceutical antiarrhythmic agent used for the medical treatment of cardiac arrhythmias. Procainamide: A class Ia antiarrhythmic drug that is structurally-related to PROCAINE. | benzamides | anti-arrhythmia drug; platelet aggregation inhibitor; sodium channel blocker |
2-phenylcyclopropan-1-amine | 2-phenylcyclopropan-1-amine : A member of the class of cyclopropanes carrying amino and phenyl substituents at positions 1 and 2 respectively. | benzenes; cyclopropanes; primary amine | |
dichlone | dichlone: structure | ||
5,5'-methylenedisalicylic acid | 5,5'-methylenedisalicylic acid: inhibits attachment of ribosomes to microsomal membranes; RN given refers to parent cpd; structure in first source & Merck Index, 9th ed, #5934 | ||
rg108 | RG108: DNA methyltransferase inhibitor; structure in first source | indolyl carboxylic acid | |
(1R,2S)-tranylcypromine hydrochloride | (1R,2S)-tranylcypromine hydrochloride : A hydrochloride obtained by combining (1R,2S)-tranylcypromine with one equivalent of hydrochloric acid. | hydrochloride | |
genistein | 7-hydroxyisoflavones | antineoplastic agent; EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor; geroprotector; human urinary metabolite; phytoestrogen; plant metabolite; tyrosine kinase inhibitor | |
sgi-1027 | SGI-1027: inhibits DNA methyltransferase 1; structure in first source | ||
gsk2879552 | GSK2879552 : A member of the class of piperidines that is piperidine substituted by (4-carboxyphenyl)methyl and {[(1R,2S)-2-phenylcyclopropyl]amino}methyl groups at positions 1 and 4, respectively. It is a potent and irreversible inhibitor of lysine specific demethylase 1 (LSD1, also known as KDM1A). It was under clinical investigation for the treatment of acute myeloid leukaemia and small cell lung carcinoma. GSK2879552: inhibits lysine demethylase 1; structure in first source | benzenes; benzoic acids; cyclopropanes; monocarboxylic acid; piperidines; secondary amino compound; tertiary amino compound | antineoplastic agent; EC 1.14.99.66 (lysine-specific histone demethylase 1A) inhibitor |