histone H3K9 trimethyltransferase activity
Definition
Target type: molecularfunction
Catalysis of the reaction: L-lysyl9-[histone H3] + 3 S-adenosyl-L-methionine = 3 H+ + N6,N6,N6-trimethyl-L-lysyl9-[histone H3] + 3 S-adenosyl-L-homocysteine. This reaction is the successive addition of three methyl groups to the unmethylated lysine residue at position 9 of histone H3, producing histone H3K9me3. [RHEA:60276]
Histone H3K9 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 9 residue of histone H3. This process is crucial for the establishment and maintenance of heterochromatin, a highly condensed and transcriptionally inactive form of chromatin.
Specifically, trimethylation of histone H3 at lysine 9 (H3K9me3) serves as a docking site for heterochromatin protein 1 (HP1), a key factor in heterochromatin formation. HP1 binding to H3K9me3 promotes the recruitment of additional HP1 molecules, leading to a self-propagating mechanism that further compacts chromatin.
This compaction restricts access of transcription factors and other regulatory proteins to DNA, effectively silencing gene expression.
Furthermore, H3K9 trimethylation plays a role in various cellular processes, including:
- **Chromosomal stability:** H3K9me3 contributes to the structural integrity of chromosomes by ensuring proper segregation during cell division.
- **DNA replication:** H3K9 methylation patterns are re-established after DNA replication, ensuring proper inheritance of epigenetic information.
- **Development:** H3K9 methylation patterns are dynamically regulated during development, contributing to cell differentiation and tissue formation.
- **Immune response:** H3K9 trimethylation is involved in silencing transposons and repetitive elements, preventing their uncontrolled expression and potential disruption of the genome.
Aberrant H3K9 trimethylation is linked to various diseases, including cancer. Overexpression of H3K9 trimethyltransferases can lead to inappropriate gene silencing, contributing to tumorigenesis. Conversely, decreased H3K9 trimethylation can result in genomic instability and increased susceptibility to cancer.
Therefore, H3K9 trimethyltransferase activity is essential for maintaining genome integrity, regulating gene expression, and orchestrating a variety of cellular processes.'
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Proteins (3)
| Protein | Definition | Taxonomy |
|---|---|---|
| Histone-lysine N-methyltransferase SUV39H2 | A histone-lysine N-methyltransferase SUV39H2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9H5I1] | Homo sapiens (human) |
| Histone-lysine N-methyltransferase SETDB1 | A histone-lysine N-methyltransferase SETDB1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q15047] | Homo sapiens (human) |
| Histone-lysine N-methyltransferase SUV39H1 | A histone-lysine N-methyltransferase SUV39H1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O43463] | Homo sapiens (human) |
Compounds (6)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| gliotoxin | gliotoxin : 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 |
| 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 |
| verticillins | verticillins: 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 | |||
| 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 |
| 6,7-dimethoxy-2-(pyrrolidin-1-yl)-n-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine | 6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine: a SETD8 inhibitor; structure in first source |