pericentric heterochromatin formation
Definition
Target type: biologicalprocess
The compaction of chromatin located adjacent to the CENP-A rich centromere 'central core' and characterized by methylation of histone H3K9, into heterochromatin, resulting in the repression of transcription at pericentric DNA. [GOC:mah, PMID:14612388, PMID:20206496, PMID:22729156]
Pericentric heterochromatin is a specialized type of chromatin that forms at the centromeres of chromosomes, the constricted regions that attach to microtubules during cell division. Its formation involves a complex interplay of DNA sequences, proteins, and modifications.
First, pericentric regions are enriched in repetitive DNA sequences, such as satellite DNA, which are highly conserved but non-coding. These repetitive sequences are thought to contribute to the formation of heterochromatin by facilitating the binding of specific proteins.
One such protein is HP1, a key player in heterochromatin formation. HP1 binds to methylated lysine 9 on histone H3 (H3K9me), a histone modification that is characteristic of heterochromatin. This binding recruits other proteins, including chromatin remodelers and histone methyltransferases, to the pericentric region.
Chromatin remodelers alter the structure of chromatin, making it more compact and inaccessible to transcription factors. Histone methyltransferases further reinforce the heterochromatic state by adding more methyl groups to H3K9. This cascade of events ultimately leads to the formation of a dense, tightly packed chromatin structure that is transcriptionally inactive.
The formation of pericentric heterochromatin is essential for proper chromosome segregation during cell division. It ensures that centromeres attach correctly to microtubules, preventing chromosome missegregation and aneuploidy. Additionally, pericentric heterochromatin plays a role in silencing genes located near centromeres, which could potentially disrupt chromosome function.
The process of pericentric heterochromatin formation is tightly regulated and can vary between different organisms and cell types. However, the basic principles of repetitive DNA sequences, protein recruitment, and histone modifications remain largely conserved.'
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Proteins (1)
| Protein | Definition | Taxonomy |
|---|---|---|
| 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) |
Compounds (9)
| 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 |
| 1-(4-nitrophenyl)piperazine | 1-(4-nitrophenyl)piperazine: structure in first source | ||
| 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 |
| 5-chloropyrazinamide | |||
| 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 |
| (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) | |
| ly2784544 | pyridazines |