Page last updated: 2024-10-24

negative regulation of rDNA heterochromatin formation

Definition

Target type: biologicalprocess

Any process that decreases the rate, frequency, or extent of ribosomal DNA heterochromatin formation. [GOC:dph, PMID:10388812]

Negative regulation of rDNA heterochromatin formation is a crucial process that ensures proper ribosomal RNA (rRNA) transcription and ribosome biogenesis. Heterochromatin, a densely packed form of chromatin, is typically associated with gene silencing. In the case of ribosomal DNA (rDNA), which encodes rRNA, inappropriate heterochromatin formation would lead to decreased rRNA production, impacting protein synthesis and cellular function.

Here is a detailed breakdown of the process:

**1. Factors Influencing rDNA Heterochromatin Formation:**
- **Histone Modifications:** Specific histone modifications, such as methylation of histone H3 at lysine 9 (H3K9me) and lysine 27 (H3K27me), are associated with heterochromatin formation.
- **DNA Methylation:** Methylation of cytosine bases in DNA can contribute to the recruitment of proteins involved in heterochromatin formation.
- **Non-coding RNAs (ncRNAs):** Small RNAs, such as siRNA and piRNA, can target rDNA loci and promote heterochromatin formation.

**2. Mechanisms of Negative Regulation:**
- **Histone Deacetylases (HDACs):** These enzymes remove acetyl groups from histone tails, promoting a more condensed chromatin state. Negative regulation involves inhibiting HDAC activity at rDNA loci.
- **Histone Methyltransferases (HMTs):** These enzymes add methyl groups to histones. Negative regulation involves inhibiting HMTs that promote H3K9me or H3K27me at rDNA.
- **Chromatin Remodeling Complexes:** These complexes can reposition nucleosomes, altering the accessibility of DNA. Negative regulation involves activating chromatin remodeling complexes that promote an open chromatin conformation at rDNA.
- **Transcription Factors:** Specific transcription factors can bind to rDNA and promote transcription, counteracting heterochromatin formation.

**3. Importance of Negative Regulation:**
- **Ribosome Biogenesis:** Proper rRNA transcription is essential for ribosome assembly, which is vital for protein synthesis.
- **Cellular Growth and Development:** The negative regulation of rDNA heterochromatin formation ensures that cells can produce sufficient ribosomes to meet their needs.
- **Genome Stability:** The proper regulation of rDNA structure helps prevent aberrant recombination events that can destabilize the genome.'
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Proteins (2)

ProteinDefinitionTaxonomy
Histone lysine demethylase PHF8A histone lysine demethylase PHF8 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9UPP1]Homo sapiens (human)
Lysine-specific demethylase PHF2A lysine-specific demethylase PHF2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O75151]Homo sapiens (human)

Compounds (6)

CompoundDefinitionClassesRoles
amiodaroneamiodarone : A member of the class of 1-benzofurans that is 1-benzofuran substituted by a butyl group at position 2 and a 4-[2-(diethylamino)ethoxy]-3,5-diiodobenzoyl group at position 3. It is a cardiovascular drug used for the treatment of cardiac dysrhythmias.

Amiodarone: An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.
1-benzofurans;
aromatic ketone;
organoiodine compound;
tertiary amino compound
cardiovascular drug
succinylacetone4,6-dioxoheptanoic acid : A dioxo monocarboxylic acid that is heptanoic acid in which oxo groups replace the hydrogens at positions 4 and 6. It is an abnormal metabolite of the tyrosine metabolic pathway and a marker for type 1 tyrosinaemia.

succinylacetone: inhibitor of heme biosynthesis
beta-diketone;
dioxo monocarboxylic acid
human metabolite
2,4-pyridinedicarboxylic acidlutidinic acid : A pyridinedicarboxylic acid carrying carboxy groups at positions 2 and 4.pyridinedicarboxylic acid
daminozidedaminozide: induces tumorsstraight-chain fatty acid
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
3-[[2-(2-pyridinyl)-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-4-pyrimidinyl]amino]propanoic acidorganonitrogen heterocyclic compound