Target type: molecularfunction
Catalysis of the reaction: L-lysyl27-[histone H3] + 3 S-adenosyl-L-methionine = 3 H+ + N6,N6,N6-trimethyl-L-lysyl27-[histone H3] + 3 S-adenosyl-L-homocysteine. This reaction is the successive addition of three methyl groups to the unmethylated lysine residue at position 27 of histone H3, producing histone H3K27me3. [RHEA:60292]
Histone H3K27 trimethyltransferase activity refers to the enzymatic ability to catalyze the transfer of three methyl groups from a donor molecule, typically S-adenosyl methionine (SAM), to the lysine residue at position 27 (K27) of histone H3. This specific methylation event plays a pivotal role in the regulation of gene expression, primarily by acting as a repressive mark.
Histone H3K27 trimethylation (H3K27me3) is associated with the silencing of genes, primarily by facilitating the recruitment of Polycomb repressive complex 2 (PRC2), a multi-protein complex that further promotes gene silencing. PRC2 is a key regulator of developmental processes, and its dysregulation is implicated in various diseases, including cancer.
The mechanism by which H3K27me3 mediates gene silencing involves several factors:
1. **Chromatin compaction:** H3K27me3 contributes to the compaction of chromatin, making the DNA less accessible to transcription factors and other regulatory proteins, thus hindering gene expression.
2. **Recruitment of repressive complexes:** H3K27me3 acts as a docking site for various chromatin-modifying enzymes, including the PRC2 complex itself. This recruitment allows for the propagation of repressive marks and the establishment of a repressive chromatin environment.
3. **Interaction with other repressive factors:** H3K27me3 can interact with other repressive proteins, like HP1α, further enhancing gene silencing.
4. **Regulation of developmental pathways:** H3K27me3 is essential for regulating the expression of genes involved in developmental processes, ensuring proper differentiation and cell fate determination.
The intricate molecular function of histone H3K27 trimethyltransferase activity highlights its crucial role in maintaining genomic integrity, regulating gene expression, and controlling developmental pathways. Aberrant activity of this enzyme is linked to various diseases, emphasizing its importance in human health.'
"
| Protein | Definition | Taxonomy |
|---|---|---|
| Histone-lysine N-methyltransferase EZH1 | A histone-lysine N-methyltransferase EZH1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q92800] | Homo sapiens (human) |
| Histone-lysine N-methyltransferase EZH2 | A histone-lysine N-methyltransferase EZH2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q15910] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| 3-deazaneplanocin | 3-deazaneplanocin: S-adenosylhomocysteine hydrolase antagonist | ||
| tanshinone | tanshinone: from root of Salvia miltiorrhiza Bunge; RN given refers to tanshinone I; cardioprotective agent and neuroprotective agent | abietane diterpenoid | anticoronaviral agent |
| przewaquinone d | przewaquinone D: isolated from root of Salvia przewalskii; structure given in first source; RN given refers to the trans- isomer, przewaquinone D | ||
| tanshinone ii a | tashinone IIA: a cardiovascular agent with antineoplastic activity; isolated from Salvia miltiorrhiza; structure in first source | abietane diterpenoid | |
| s-adenosylhomocysteine | S-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 |
| scutellarein | scutellarein : Flavone substituted with hydroxy groups at C-4', -5, -6 and -7. scutellarein: aglycone of scutellarin from Scutellaria baicalensis; carthamidin is 2S isomer of scutellarein; do not confuse with isoscutellarein and/or isocarthamidin which are respective regioisomers, or with the scutelarin protein | tetrahydroxyflavone | metabolite |
| epz005687 | EPZ005687: inhibits EZH2 protein; structure in first source | indazoles | |
| epz-6438 | tazemetostat: a histone methyltransferase EZH2 inhibitor with antineoplastic activity | ||
| gsk-2816126 | GSK-2816126: inhibits EZH2 methyltransferase; structure in first source | piperazines; pyridines | |
| gsk343 | GSK343 : 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 |
| 1-[(1R)-1-(1-ethylsulfonyl-4-piperidinyl)ethyl]-N-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-2-methyl-3-indolecarboxamide | (R)-1-(1-(1-(ethylsulfonyl)piperidin-4-yl)ethyl)-N-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1H-indole-3-carboxamide: EZH2 inhibitor | indolecarboxamide |