Page last updated: 2024-10-24

pericentric heterochromatin

Definition

Target type: cellularcomponent

Heterochromatin that is located adjacent to the CENP-A rich centromere 'central core' and characterized by methylated H3 histone at lysine 9 (H3K9me2/H3K9me3). [PMID:12019236, PMID:20206496, PMID:21437270, PMID:22729156, PMID:9413993]

Pericentric heterochromatin is a specialized region of chromatin located near the centromere of chromosomes. It is characterized by its densely packed structure, which is largely due to the high content of repetitive DNA sequences. The cellular component of pericentric heterochromatin is complex and dynamic, encompassing various proteins, RNAs, and DNA modifications.

**Key Components:**

1. **DNA:** Pericentric heterochromatin is enriched in repetitive DNA sequences, including satellite DNA, transposons, and other repetitive elements. These sequences are highly conserved and often lack protein-coding genes.

2. **Histones:** Histones are the primary protein components of chromatin. In pericentric heterochromatin, histone modifications play a crucial role in establishing and maintaining its condensed structure. These modifications include:
- **H3K9me3:** Trimethylation of lysine 9 on histone H3, a hallmark of heterochromatin. This modification is catalyzed by histone methyltransferases like SUV39H1 and G9a.
- **H4K20me3:** Trimethylation of lysine 20 on histone H4, another repressive mark associated with heterochromatin.

3. **Heterochromatin Protein 1 (HP1):** HP1 is a key protein involved in the formation and maintenance of heterochromatin. It binds to H3K9me3 and promotes further condensation of chromatin.

4. **Other Proteins:** Several other proteins contribute to the formation and function of pericentric heterochromatin, including:
- **CENP-A:** A specialized histone variant that is specifically localized to centromeres and plays a role in kinetochore assembly.
- **Cohesin:** A protein complex involved in sister chromatid cohesion during mitosis.
- **Topoisomerase II:** An enzyme that regulates DNA topology and facilitates chromatin condensation.

5. **Non-coding RNAs:** Non-coding RNAs, such as long non-coding RNAs (lncRNAs), are emerging as important regulators of heterochromatin formation and function. Some lncRNAs have been shown to interact with HP1 and other heterochromatin proteins.

6. **DNA Modifications:** DNA methylation is another important epigenetic modification associated with heterochromatin. Methylation of CpG dinucleotides is generally found to be higher in pericentric heterochromatin, further contributing to its condensed structure.

**Functions:**

Pericentric heterochromatin plays essential roles in cellular processes, including:

1. **Chromosome Segregation:** The condensed nature of pericentric heterochromatin helps ensure proper chromosome segregation during cell division. It provides a stable platform for kinetochore assembly and prevents the entanglement of chromosomes.

2. **Gene Regulation:** Pericentric heterochromatin is generally associated with gene silencing. The dense structure of heterochromatin inhibits access of transcriptional machinery to DNA, effectively silencing genes located within these regions.

3. **Genome Stability:** Pericentric heterochromatin is thought to contribute to genome stability by preventing the spread of transposable elements and other repetitive DNA sequences.

4. **Development:** Pericentric heterochromatin can be dynamically regulated during development, playing a role in tissue-specific gene expression and cell differentiation.

**Disruptions:**

Disruptions in pericentric heterochromatin structure or function can lead to various cellular defects and diseases, including:

1. **Chromosomal Instability:** Aberrant heterochromatin formation can lead to chromosome missegregation and aneuploidy, contributing to developmental abnormalities and cancer.

2. **Gene Misregulation:** Changes in heterochromatin organization can alter gene expression patterns, potentially leading to developmental disorders or disease susceptibility.

3. **Premature Senescence:** Pericentric heterochromatin is linked to cellular senescence, a state of irreversible cell cycle arrest. Aberrant heterochromatin formation may contribute to premature aging.

In summary, pericentric heterochromatin is a dynamic and essential cellular component that plays crucial roles in chromosome segregation, gene regulation, genome stability, and development. Its complex composition and regulation make it a fascinating area of ongoing research.'
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Proteins (9)

ProteinDefinitionTaxonomy
Inner centromere proteinAn inner centromere protein that is encoded in the genome of human. [PRO:KER]Homo sapiens (human)
Lysine-specific demethylase 4CA lysine-specific demethylase 4C that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9H3R0]Homo sapiens (human)
NAD-dependent protein deacetylase sirtuin-6An NAD-dependent protein deacylase sirtuin-6 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q8N6T7]Homo sapiens (human)
Histone-lysine N-methyltransferase KMT5CA histone-lysine N-methyltransferase KMT5C that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q86Y97]Homo sapiens (human)
Lysine-specific demethylase 4DA lysine-specific demethylase 4D that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q6B0I6]Homo sapiens (human)
Histone-lysine N-methyltransferase EZH2A histone-lysine N-methyltransferase EZH2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q15910]Homo sapiens (human)
DNA-binding protein IkarosA DNA-binding protein Ikaros that is encoded in the genome of human. [PRO:WCB, UniProtKB:Q13422]Homo sapiens (human)
DNA (cytosine-5)-methyltransferase 1A DNA (cytosine-5)-methyltransferase 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P26358]Homo sapiens (human)
Lysine-specific demethylase 4AA lysine-specific demethylase 4A that is encoded in the genome of human. [PRO:DNx, UniProtKB:O75164]Homo sapiens (human)

Compounds (69)

CompoundDefinitionClassesRoles
niacinamidenicotinamide : 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
pyrazinamidepyrazinecarboxamide : 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 acidpyrazine-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 acidantitubercular agent;
drug metabolite
pyrazole1H-pyrazole : The 1H-tautomer of pyrazole.pyrazole
deferipronedeferiprone : A member of the class of 4-pyridones that is pyridin-4(1H)-one substituted at positions 1 and 2 by methyl groups and at position 3 by a hydroxy group. A lipid-soluble iron-chelator used for treatment of thalassaemia.

Deferiprone: A pyridone derivative and iron chelator that is used in the treatment of IRON OVERLOAD in patients with THALASSEMIA.
4-pyridonesiron chelator;
protective agent
deferoxamineDeferoxamine: Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the mesylate form.

desferrioxamine B : An acyclic desferrioxamine that is butanedioic acid in which one of the carboxy groups undergoes formal condensation with the primary amino group of N-(5-aminopentyl)-N-hydroxyacetamide and the second carboxy group undergoes formal condensation with the hydroxyamino group of N(1)-(5-aminopentyl)-N(1)-hydroxy-N(4)-[5-(hydroxyamino)pentyl]butanediamide. It is a siderophore native to Streptomyces pilosus biosynthesised by the DesABCD enzyme cluster as a high affinity Fe(III) chelator.
acyclic desferrioxaminebacterial metabolite;
ferroptosis inhibitor;
iron chelator;
siderophore
amrinoneamrinone : A 3,4'-bipyridine substituted at positions 5 and 6 by an amino group and a keto function respectively. A pyridine phosphodiesterase 3 inhibitor, it is a drug that may improve the prognosis in patients with congestive heart failure.

Amrinone: A positive inotropic cardiotonic (CARDIOTONIC AGENTS) with vasodilator properties, phosphodiesterase 3 inhibitory activity, and the ability to stimulate calcium ion influx into the cardiac cell.
bipyridinesEC 3.1.4.* (phosphoric diester hydrolase) inhibitor
milrinonebipyridines;
nitrile;
pyridone
cardiotonic drug;
EC 3.1.4.17 (3',5'-cyclic-nucleotide phosphodiesterase) inhibitor;
platelet aggregation inhibitor;
vasodilator agent
nitrazepamnitrazepam : A 1,4-benzodiazepinone that is 1,3-dihydro-2H-1,4-benzodiazepin-2-one which is substituted at positions 5 and 7 by phenyl and nitro groups, respectively. It is used as a hypnotic for the short-term management of insomnia and for the treatment of epileptic spasms in infants (West's syndrome).

Nitrazepam: A benzodiazepine derivative used as an anticonvulsant and hypnotic.
1,4-benzodiazepinone;
C-nitro compound
anticonvulsant;
antispasmodic drug;
drug metabolite;
GABA modulator;
sedative
procainamideprocainamide : 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.
benzamidesanti-arrhythmia drug;
platelet aggregation inhibitor;
sodium channel blocker
vorinostatvorinostat : A dicarboxylic acid diamide comprising suberic (octanedioic) acid coupled to aniline and hydroxylamine. A histone deacetylase inhibitor, it is marketed under the name Zolinza for the treatment of cutaneous T cell lymphoma (CTCL).

Vorinostat: A hydroxamic acid and anilide derivative that acts as a HISTONE DEACETYLASE inhibitor. It is used in the treatment of CUTANEOUS T-CELL LYMPHOMA and SEZARY SYNDROME.
dicarboxylic acid diamide;
hydroxamic acid
antineoplastic agent;
apoptosis inducer;
EC 3.5.1.98 (histone deacetylase) inhibitor
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
dichlonedichlone: structure
azacitidine5-azacytidine : An N-glycosyl-1,3,5-triazine that is 4-amino-1,3,5-triazin-2(1H)-one substituted by a beta-D-ribofuranosyl residue via an N-glycosidic linkage. An antineoplastic agent, it is used in the treatment of myeloid leukaemia.

Azacitidine: A pyrimidine analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent.
N-glycosyl-1,3,5-triazine;
nucleoside analogue
antineoplastic agent
2,4-pyridinedicarboxylic acidlutidinic acid : A pyridinedicarboxylic acid carrying carboxy groups at positions 2 and 4.pyridinedicarboxylic acid
daminozidedaminozide: induces tumorsstraight-chain fatty acid
epigallocatechin gallate(-)-epigallocatechin 3-gallate : A gallate ester obtained by the formal condensation of gallic acid with the (3R)-hydroxy group of (-)-epigallocatechin.

epigallocatechin gallate: a steroid 5alpha-reductase inhibitor and antimutagen in green tea (Camellia sinensis)
flavans;
gallate ester;
polyphenol
antineoplastic agent;
antioxidant;
apoptosis inducer;
geroprotector;
Hsp90 inhibitor;
neuroprotective agent;
plant metabolite
toxoflavintoxoflavin : 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
5,5'-methylenedisalicylic acid5,5'-methylenedisalicylic acid: inhibits attachment of ribosomes to microsomal membranes; RN given refers to parent cpd; structure in first source & Merck Index, 9th ed, #5934
n-acetylglutamic acidN-acetyl-L-glutamic acid : An N-acyl-L-amino acid that is L-glutamic acid in which one of the amine hydrogens is substituted by an acetyl group.

N-acetylglutamic acid: RN given refers to (L)-isomer
N-acetyl-L-amino acid;
N-acyl-L-glutamic acid
human metabolite;
Saccharomyces cerevisiae metabolite
3-deazaneplanocin3-deazaneplanocin: S-adenosylhomocysteine hydrolase antagonist
1-(4-nitrophenyl)piperazine1-(4-nitrophenyl)piperazine: structure in first source
2-(2,6-dioxopiperidin-3-yl)phthalimidine2-(2,6-dioxopiperidin-3-yl)phthalimidine: thalidomide analog; structure; RN given refers to cpd without isomeric designation
tanshinonetanshinone: from root of Salvia miltiorrhiza Bunge; RN given refers to tanshinone I; cardioprotective agent and neuroprotective agentabietane diterpenoidanticoronaviral agent
rubimaillinrubimaillin : 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
s-tubercidinylhomocysteine
di-n-desethylamiodaronedi-N-desethylamiodarone: amiodarone metabolite in dogs; structure given in first source
przewaquinone dprzewaquinone D: isolated from root of Salvia przewalskii; structure given in first source; RN given refers to the trans- isomer, przewaquinone D
6-bromo-3-(bromomethyl)-7-methyl-2,3,7-trichloro-1-octene6-bromo-3-(bromomethyl)-7-methyl-2,3,7-trichloro-1-octene: structure given in first sourcemonoterpenoid;
organobromine compound;
organochlorine compound
algal metabolite;
antineoplastic agent;
marine metabolite
pomalidomide3-aminophthalimidoglutarimide: structure in first sourcearomatic amine;
dicarboximide;
isoindoles;
piperidones
angiogenesis inhibitor;
antineoplastic agent;
immunomodulator
tanshinone ii atashinone IIA: a cardiovascular agent with antineoplastic activity; isolated from Salvia miltiorrhiza; structure in first sourceabietane diterpenoid
s-adenosyl-3-thiopropylamineS-adenosyl-3-thiopropylamine : A thioadenosine that is adenosine in which the hydroxy group at C-5' is replaced by a 3-aminopropyl group.

S-adenosyl-3-thiopropylamine: decarboxylated S-adenosylhomocysteine; RN given refers to parent cpd
organic sulfide;
primary amino compound;
thioadenosine
5-chloropyrazinamide
n(4)-adenosyl-n(4)-methyl-2,4-diaminobutanoic acid
deferasiroxdeferasirox : A member of the class of triazoles, deferasirox is 1,2,4-triazole substituted by a 4-carboxyphenyl group at position 1 and by 2-hydroxyphenyl groups at positions 3 and 5. An orally active iron chelator, it is used to manage chronic iron overload in patients receiving long-term blood transfusions.

Deferasirox: A triazole and benzoate derivative that acts as a selective iron chelator. It is used in the management of chronic IRON OVERLOAD due to blood transfusion or non-transfusion dependent THALASSEMIA.
benzoic acids;
monocarboxylic acid;
phenols;
triazoles
iron chelator
lenalidomidearomatic amine;
dicarboximide;
isoindoles;
piperidones
angiogenesis inhibitor;
antineoplastic agent;
immunomodulator
nsc 401077NSC 401077: inhibits DNA methyltransferase DNMT1; structure in first source
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
d-2-hydroxyglutarate(R)-2-hydroxyglutaric acid : The (R)-enantiomer of 2-hydroxyglutaric acid.2-hydroxyglutaric acidalgal metabolite
alpha-hydroxyglutarate, (l)-isomer2-hydroxyglutaric acid
trichostatin atrichostatin 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 STREPTOMYCESantibiotic antifungal agent;
hydroxamic acid;
trichostatin
bacterial metabolite;
EC 3.5.1.98 (histone deacetylase) inhibitor;
geroprotector
(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)
decitabine2'-deoxyribonucleoside
5-carboxy-8-hydroxyquinoline5-carboxy-8-hydroxyquinoline: a JmjC histone demethylase inhibitor; structure in first sourcequinolines
rg108RG108: DNA methyltransferase inhibitor; structure in first sourceindolyl 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
N-[2-furanyl-(8-hydroxy-7-quinolinyl)methyl]-2-methylpropanamidehydroxyquinoline
oxalylglycineN-oxalylglycine : An amino dicarboxylic acid that is iminodiacetic acid with an oxo substituent. It is used as an inhibitor of alpha-ketoglutarate dependent (EC 1.14.11.*) enzymes.

oxalylglycine: structure given in first source
amino dicarboxylic acid;
N-acylglycine
EC 1.14.11.* (oxidoreductase acting on paired donors, 2-oxoglutarate as one donor, incorporating 1 atom each of oxygen into both donors) inhibitor
genistein7-hydroxyisoflavonesantineoplastic agent;
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor;
geroprotector;
human urinary metabolite;
phytoestrogen;
plant metabolite;
tyrosine kinase inhibitor
geldanamycin1,4-benzoquinones;
ansamycin;
carbamate ester;
organic heterobicyclic compound
antimicrobial agent;
antineoplastic agent;
antiviral agent;
cysteine protease inhibitor;
Hsp90 inhibitor
17-(dimethylaminoethylamino)-17-demethoxygeldanamycin17-(dimethylaminoethylamino)-17-demethoxygeldanamycin: structure in first source

alvespimycin : A 19-membered macrocyle that is geldanamycin in which the methoxy group attached to the benzoquinone moiety has been replaced by a 2-(N,N-dimethylamino)ethylamino group.
1,4-benzoquinones;
ansamycin;
carbamate ester;
secondary amino compound;
tertiary amino compound
Hsp90 inhibitor
psammaplin apsammaplin A: isolated from marine sponges Poecillastra and Jaspis; structure in second source
tanespimycinCP 127374: analog of herbimycin A1,4-benzoquinones;
ansamycin;
carbamate ester;
organic heterobicyclic compound;
secondary amino compound
antineoplastic agent;
apoptosis inducer;
Hsp90 inhibitor
tak-901
mk 5108aromatic ether
mln 8237MLN 8237: an aurora kinase A inhibitorbenzazepine
sgi-1027SGI-1027: inhibits DNA methyltransferase 1; structure in first source
bix 01294piperidines
ly2784544pyridazines
unc 0638UNC 0638: inhibits lysine methyltransferases G9a and GLP; structure in first sourcequinazolines
gsk 1070916GSK 1070916: an antineoplastic agent with aurora B/C kinase inhibitory activitypyrazoles;
ring assembly
3-[[2-(2-pyridinyl)-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-4-pyrimidinyl]amino]propanoic acidorganonitrogen heterocyclic compound
cfi-400945
epz005687EPZ005687: inhibits EZH2 protein; structure in first sourceindazoles
epz-6438tazemetostat: a histone methyltransferase EZH2 inhibitor with antineoplastic activity
gsk-2816126GSK-2816126: inhibits EZH2 methyltransferase; structure in first sourcepiperazines;
pyridines
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
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 inhibitorindolecarboxamide
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