Target type: biologicalprocess
The compaction of chromatin into heterochromatin at the subtelomeric region. [GOC:mah, PMID:10219245, PMID:26205977]
Subtelomeric heterochromatin, located at the ends of chromosomes, is a specialized chromatin structure characterized by its unique composition and role in genome stability and regulation. Its formation is a complex process involving various factors and steps:
1. **Repetitive DNA Sequences:** Subtelomeric regions are enriched in repetitive DNA sequences, such as telomeric repeats (TTAGGG)n, and other satellite DNA sequences. These repetitive sequences are highly prone to recombination and instability.
2. **Heterochromatin Proteins:** Specific proteins, including HP1α, HP1β, and HP1γ, are recruited to subtelomeric regions. These proteins act as structural components of heterochromatin and bind to methylated histone tails (H3K9me3) which are enriched in these regions.
3. **Histone Modifications:** Histone tails within subtelomeric regions undergo specific modifications, particularly H3K9 methylation. This methylation is catalyzed by histone methyltransferases (HMTs) like Suv39h1 and G9a.
4. **DNA Methylation:** In some organisms, DNA methylation also contributes to subtelomeric heterochromatin formation. DNA methyltransferases (DNMTs) modify cytosines within the repetitive sequences.
5. **Replication Timing:** Subtelomeric regions typically replicate late in S phase. This late replication timing contributes to their compacted and inaccessible nature.
6. **Nuclear Organization:** Subtelomeric regions are often clustered together in the nucleus, forming distinct domains called "telomere clusters." This clustering facilitates interactions between telomeres and other nuclear structures.
7. **Silencing of Gene Expression:** Subtelomeric heterochromatin is associated with silencing of genes located within these regions. This silencing is mediated by the compact and inaccessible nature of heterochromatin, which prevents transcription factors from accessing the DNA.
8. **Protection from DNA Damage:** Subtelomeric heterochromatin plays a crucial role in protecting chromosome ends from degradation and fusion. The compact structure provides a barrier against exonucleases and other DNA-damaging agents.
9. **Maintenance of Telomere Length:** Subtelomeric heterochromatin is involved in regulating telomere length. It acts as a barrier against the spread of telomere repeats, ensuring proper telomere maintenance.
10. **Regulation of Gene Expression:** While subtelomeric heterochromatin is primarily associated with gene silencing, it can also influence gene expression in nearby regions. This influence can involve spreading of silencing signals or the recruitment of regulatory factors.'
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| 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) |
| NAD-dependent protein deacetylase sirtuin-6 | An NAD-dependent protein deacylase sirtuin-6 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q8N6T7] | Homo sapiens (human) |
| NAD-dependent protein deacetylase sirtuin-2 | An NAD-dependent protein deacetylase sirtuin-2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q8IXJ6] | 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 |
|---|---|---|---|
| niacinamide | nicotinamide : A pyridinecarboxamide that is pyridine in which the hydrogen at position 3 is replaced by a carboxamide group. | pyridine alkaloid; pyridinecarboxamide; vitamin B3 | anti-inflammatory agent; antioxidant; cofactor; EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor; EC 3.5.1.98 (histone deacetylase) inhibitor; Escherichia coli metabolite; geroprotector; human urinary metabolite; metabolite; mouse metabolite; neuroprotective agent; Saccharomyces cerevisiae metabolite; Sir2 inhibitor |
| pyrazinamide | pyrazinecarboxamide : A monocarboxylic acid amide resulting from the formal condensation of the carboxy group of pyrazinoic acid (pyrazine-2-carboxylic acid) with ammonia. A prodrug for pyrazinoic acid, pyrazinecarboxamide is used as part of multidrug regimens for the treatment of tuberculosis. | monocarboxylic acid amide; N-acylammonia; pyrazines | antitubercular agent; prodrug |
| pyrazinoic acid | pyrazine-2-carboxylic acid : The parent compound of the class of pyrazinecarboxylic acids, that is pyrazine bearing a single carboxy substituent. The active metabolite of the antitubercular drug pyrazinamide. pyrazinoic acid: active metabolite of pyrazinamide; structure | pyrazinecarboxylic acid | antitubercular agent; drug metabolite |
| bisindolylmaleimide i | bisindolylmaleimide I: a bis(indolyl)maleimide | ||
| 2-(1-(2-(1-methylpyrrolidino)ethyl)-1h-indol-3-yl)maleimide | bisindolylmaleimide II: protein kinase C inhibitor; see also bisindolylmaleimide I | ||
| bisindolylmaleimide iv | indoles; maleimides | ||
| bisindolylmaleimide v | bisindolylmaleimide V: used as a negative control compound for protein kinase C inhibition; structure in first source; | indoles | |
| go 6976 | indolocarbazole; organic heterohexacyclic compound | EC 2.7.11.13 (protein kinase C) inhibitor | |
| idebenone | 1,4-benzoquinones; primary alcohol | antioxidant; ferroptosis inhibitor | |
| nsc 664704 | kenpaullone : An indolobenzazepine that is paullone in which the hydrogen at position 9 is replaced by a bromo substituent. It is an ATP-competitive inhibitor of cyclin-dependent kinases (CDKs) and glycogen synthase kinase 3beta (GSK3beta). kenpaullone: inhibits CDK1/cyclin B; structure in first source | indolobenzazepine; lactam; organobromine compound | cardioprotective agent; EC 2.7.11.22 (cyclin-dependent kinase) inhibitor; EC 2.7.11.26 (tau-protein kinase) inhibitor; geroprotector |
| fenamic acid | fenamic acid : An aminobenzoic acid that is the N-phenyl derivative of anthranilic acid. It acts as a parent skeleton for the synthesis of several non-steroidal anti-inflammatory drugs. fenamic acid: has chloride and potassium channel-blocking activity; RN given refers to parent cpd | aminobenzoic acid; secondary amino compound | membrane transport modulator |
| ro 31-8220 | Ro 31-8220: a protein kinase C inhibitor | imidothiocarbamic ester; indoles; maleimides | EC 2.7.11.13 (protein kinase C) inhibitor |
| fenofibrate | benzochromenone; delta-lactone; naphtho-alpha-pyrone | platelet aggregation inhibitor; Sir2 inhibitor | |
| suramin | suramin : A member of the class of phenylureas that is urea in which each of the amino groups has been substituted by a 3-({2-methyl-5-[(4,6,8-trisulfo-1-naphthyl)carbamoyl]phenyl}carbamoyl)phenyl group. An activator of both the rabbit skeletal muscle RyR1 and sheep cardiac RyR2 isoform ryanodine receptor channels, it has been used for the treatment of human African trypanosomiasis for over 100 years. Suramin: A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties. | naphthalenesulfonic acid; phenylureas; secondary carboxamide | angiogenesis inhibitor; antinematodal drug; antineoplastic agent; apoptosis inhibitor; EC 2.7.11.13 (protein kinase C) inhibitor; GABA antagonist; GABA-gated chloride channel antagonist; purinergic receptor P2 antagonist; ryanodine receptor agonist; trypanocidal drug |
| suramin sodium | suramin sodium : An organic sodium salt that is the hexasodium salt of suramin. It is an FDA approved drug for African sleeping sickness and river blindness. | organic sodium salt | angiogenesis inhibitor; antinematodal drug; antineoplastic agent; apoptosis inhibitor; EC 2.7.11.13 (protein kinase C) inhibitor; GABA antagonist; GABA-gated chloride channel antagonist; purinergic receptor P2 antagonist; ryanodine receptor agonist; trypanocidal drug |
| toxoflavin | toxoflavin : A pyrimidotriazine that is 1,6-dimethyl-1,5,6,7-tetrahydropyrimido[5,4-e][1,2,4]triazine with oxo groups at positions 5 and 7. toxoflavin: azapteridine antibiotic; structure | carbonyl compound; pyrimidotriazine | antibacterial agent; antineoplastic agent; apoptosis inducer; bacterial metabolite; toxin; virulence factor; Wnt signalling inhibitor |
| 3-deazaneplanocin | 3-deazaneplanocin: S-adenosylhomocysteine hydrolase antagonist | ||
| 1-(4-nitrophenyl)piperazine | 1-(4-nitrophenyl)piperazine: structure in first source | ||
| tanshinone | tanshinone: from root of Salvia miltiorrhiza Bunge; RN given refers to tanshinone I; cardioprotective agent and neuroprotective agent | abietane diterpenoid | anticoronaviral agent |
| rubimaillin | rubimaillin : A benzochromene that is 2H-benzo[h]chromene which is substituted by two methyl groups at position 2, a methoxycarbonyl group at position 5, and a hydroxy group at position 6. Found in the Chinese medical plant Rubia cordifola, It has an anti-cancer effect by inhibition of TNF-alpha-induced NF-kappaB activation. It is also a dual inhibitor of acyl-CoA:cholesterol acyltransferase 1 and 2 (ACAT1 and ACAT2), but is more selective for the ACAT2 isozyme. rubimaillin: structure given in first source | benzochromene; methyl ester; phenols | acyl-CoA:cholesterol acyltransferase 2 inhibitor; anti-inflammatory agent; antineoplastic agent; apoptosis inducer; neuroprotective agent; NF-kappaB inhibitor; plant metabolite |
| 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 | |
| 5-chloropyrazinamide | |||
| paullone | paullone : An indolobenzazepine that is 5,6,7,12-tetrahydroindolo[3,2-d][1]benzazepine carrying an oxo substituent at position 6. paullone: structure in first source | indolobenzazepine; lactam | EC 2.7.11.22 (cyclin-dependent kinase) inhibitor; EC 2.7.11.26 (tau-protein kinase) 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 |
| hyperforin | hyperforin : A cyclic terpene ketone that is a prenylated carbobicyclic acylphloroglucinol derivative produced by St. John's Wort, Hypericum perforatum. hyperforin: a prenylated acylphloroglucinol derivative; antibiotic component of novoimanine; psychoactive agent in St. John's wort; Russian; structure; | ||
| trichostatin a | trichostatin A: chelates zinc ion in the active site of histone deacetylases, resulting in preventing histone unpacking so DNA is less available for transcription; do not confuse with TRICHOSANTHIN which is a protein; found in STREPTOMYCES | antibiotic antifungal agent; hydroxamic acid; trichostatin | bacterial metabolite; EC 3.5.1.98 (histone deacetylase) inhibitor; geroprotector |
| resveratrol | trans-resveratrol : A resveratrol in which the double bond has E configuration. | resveratrol | antioxidant; phytoalexin; plant metabolite; quorum sensing inhibitor; radical scavenger |
| (3R,5S)-fluvastatin | (3R,5S)-fluvastatin : A (6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3,5-dihydroxyhept-6-enoic acid diastereoisomer in which the stereocentres beta- and delta- to the carboxy group have R and S configuration, respectively. The drug fluvastatin is an equimolar mixture of this compound and its enantiomer. | (6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3,5-dihydroxyhept-6-enoic acid; statin (synthetic) | |
| 3-(1-azepanylsulfonyl)-n-(3-bromphenyl)benzamide | 3-(1-azepanylsulfonyl)-N-(3-bromphenyl)benzamide: a sirtuin 2 inhibitor; structure in first source | ||
| 1,4-bis[2-(4-hydroxyphenyl)ethylamino]anthracene-9,10-dione | anthraquinone | ||
| sirtinol | aldimine; benzamides; naphthols | anti-inflammatory agent; EC 3.5.1.98 (histone deacetylase) inhibitor; Sir2 inhibitor | |
| cambinol | cambinol: inhibitor of human silent information regulator 2 enzymes; structure in first source | ||
| (4-chlorophenyl)-[4-(8-nitro-5-quinolinyl)-1-piperazinyl]methanone | N-arylpiperazine | ||
| ex 527 | 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide : A member of the class of carbazoles that is 2,3,4,9-tetrahydro-1H-carbazole which is substituted at position 1 by an aminocarbohyl group and at position 6 by a chlorine. 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide: structure in first source | carbazoles; monocarboxylic acid amide; organochlorine compound | |
| 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 |
| su 11248 | monocarboxylic acid amide; pyrroles | angiogenesis inhibitor; antineoplastic agent; EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor; immunomodulator; neuroprotective agent; vascular endothelial growth factor receptor antagonist | |
| panobinostat | panobinostat : A hydroxamic acid obtained by formal condensation of the carboxy group of (2E)-3-[4-({[2-(2-methylindol-3-yl)ethyl]amino}methyl)phenyl]prop-2-enoic acid with the amino group of hydroxylamine. A histone deacetylase inhibitor used (as its lactate salt) in combination with bortezomib and dexamethasone for the treatment of multiple myeloma. Panobinostat: An indole and hydroxamic acid derivative that acts as a HISTONE DEACETYLASE inhibitor. It is used as an antineoplastic agent in combination with BORTEZOMIB and DEXAMETHASONE for the treatment of MULTIPLE MYELOMA. | cinnamamides; hydroxamic acid; methylindole; secondary amino compound | angiogenesis modulating agent; antineoplastic agent; EC 3.5.1.98 (histone deacetylase) inhibitor |
| oblongifolin c | oblongifolin C: has antineoplastic activity; isolated from Garcinia yunnanensis; structure in first source | ||
| quisinostat | indoles | ||
| srt1460 | SRT1460: small molecule activator of SIRT1 as therapeutics for the treatment of type 2 diabetes; structure in first source | ||
| srt1720 | |||
| srt2183 | SRT2183: small molecule activator of SIRT1 as therapeutics for the treatment of type 2 diabetes; structure in first source | ||
| tenovin-6 | tenovin-6 : A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 5-(dimethylamino)pentanoic acid with the aromatic amino group of N-[(4-aminophenyl)carbamothioyl]-4-tert-butylbenzamide. | monocarboxylic acid amide; tertiary amino compound; thioureas | antineoplastic agent; p53 activator; Sir2 inhibitor |
| ly2784544 | pyridazines | ||
| acy-1215 | ricolinostat: an HDAC6 inhibitor; structure in first source | pyrimidinecarboxylic acid | |
| 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 | |
| aristoforin | Aristoforin: derivative of hyperforin, is a potent anticancer agent; structure in first source | ||
| n-(3-((2-hydroxynaphthalen-1-ylmethylene)amino)phenyl)-2-phenylpropionamide |