Page last updated: 2024-10-24

H3K9me3 modified histone binding

Definition

Target type: molecularfunction

Binding to a histone H3 in which the lysine residue at position 9 has been modified by trimethylation. [PMID:30110338]

H3K9me3 is a histone modification that plays a crucial role in regulating gene expression, primarily through its association with heterochromatin formation and transcriptional silencing. The tri-methylation of lysine 9 on histone H3 (H3K9me3) serves as a binding site for a specific class of proteins known as chromodomain proteins. These proteins contain a conserved chromodomain that recognizes and binds to the methylated lysine residue.

The binding of chromodomain proteins to H3K9me3 initiates a cascade of events that ultimately leads to the formation of heterochromatin. Heterochromatin is a tightly packed, transcriptionally inactive form of chromatin characterized by its dense structure and the absence of active genes.

The molecular function of H3K9me3 modified histone binding can be summarized as follows:

1. **Chromatin Compaction:** Chromodomain proteins bound to H3K9me3 recruit other chromatin-modifying enzymes, such as histone deacetylases (HDACs), which remove acetyl groups from histone tails. Deacetylation of histones further compacts chromatin, making it inaccessible to transcription factors and RNA polymerase.
2. **Recruitment of Heterochromatin Proteins:** H3K9me3 binding also attracts other proteins involved in heterochromatin formation, including HP1 proteins (heterochromatin protein 1). HP1 proteins bind to H3K9me3 and interact with each other, promoting the spreading of heterochromatin along the chromosome.
3. **Silencing Gene Expression:** The formation of heterochromatin effectively silences gene expression within the region. This silencing is achieved by preventing the binding of transcription factors and RNA polymerase to the DNA, thus inhibiting the initiation of transcription.

In summary, H3K9me3 modified histone binding serves as a molecular "bookmark" that attracts specific proteins, leading to chromatin compaction, heterochromatin formation, and ultimately, transcriptional silencing. This intricate molecular mechanism plays a vital role in regulating gene expression and maintaining genome stability.'
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Proteins (2)

ProteinDefinitionTaxonomy
Lysine-specific demethylase 4CA lysine-specific demethylase 4C that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9H3R0]Homo sapiens (human)
E3 ubiquitin-protein ligase UHRF1An E3 ubiquitin-protein ligase UHRF1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q96T88]Homo sapiens (human)

Compounds (18)

CompoundDefinitionClassesRoles
pyrazole1H-pyrazole : The 1H-tautomer of pyrazole.pyrazole
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
2,4-pyridinedicarboxylic acidlutidinic acid : A pyridinedicarboxylic acid carrying carboxy groups at positions 2 and 4.pyridinedicarboxylic acid
daminozidedaminozide: induces tumorsstraight-chain fatty acid
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
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
d-2-hydroxyglutarate(R)-2-hydroxyglutaric acid : The (R)-enantiomer of 2-hydroxyglutaric acid.2-hydroxyglutaric acidalgal metabolite
alpha-hydroxyglutarate, (l)-isomer2-hydroxyglutaric acid
5-carboxy-8-hydroxyquinoline5-carboxy-8-hydroxyquinoline: a JmjC histone demethylase inhibitor; structure in first sourcequinolines
(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
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
tanespimycinCP 127374: analog of herbimycin A1,4-benzoquinones;
ansamycin;
carbamate ester;
organic heterobicyclic compound;
secondary amino compound
antineoplastic agent;
apoptosis inducer;
Hsp90 inhibitor
(5-bromo-3-pyridinyl)-[4-(1-pyrrolidinyl)-1-piperidinyl]methanonearomatic carboxylic acid;
pyridinemonocarboxylic acid
3-[[2-(2-pyridinyl)-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-4-pyrimidinyl]amino]propanoic acidorganonitrogen heterocyclic compound
entecavirbenzamides;
N-acylpiperidine