regulatory ncRNA-mediated heterochromatin formation

Definition

Target type: biologicalprocess

A heterochromatin formation-based gene silencing process mediated by a regulatory non-coding RNA molecule that occur before the beginnning of trancription. [PMID:19239886, PMID:21420348]

Regulatory non-coding RNAs (ncRNAs) play a crucial role in heterochromatin formation, a process that involves the packaging of DNA into a tightly condensed state. Heterochromatin is generally transcriptionally inactive and is essential for maintaining genome stability, regulating gene expression, and controlling chromosome structure.

ncRNAs can contribute to heterochromatin formation through various mechanisms:

1. **Recruitment of chromatin modifying enzymes:** Some ncRNAs directly interact with proteins that modify chromatin structure, such as histone methyltransferases (HMTs), histone deacetylases (HDACs), and DNA methyltransferases (DNMTs). These enzymes can catalyze specific modifications on histones and DNA, respectively, which are characteristic of heterochromatin. For example, the ncRNA Xist is crucial for X chromosome inactivation in mammals. It recruits the PRC2 complex, a histone methyltransferase, to the inactive X chromosome, leading to the methylation of histone H3 at lysine 27 (H3K27me3), a hallmark of heterochromatin.

2. **Scaffolding for chromatin complexes:** ncRNAs can act as scaffolds, bringing together multiple proteins involved in heterochromatin formation. This can facilitate the assembly of large protein complexes that modify chromatin structure and repress gene expression. For instance, the ncRNA HOTAIR interacts with both the PRC2 and LSD1 complexes, bringing them to specific genomic regions and promoting the formation of repressive heterochromatin.

3. **Direct interaction with DNA:** Some ncRNAs can bind directly to DNA, influencing the accessibility of the DNA to transcription factors and other regulatory proteins. This interaction can stabilize or destabilize chromatin structure, depending on the specific ncRNA and its target DNA sequence.

4. **Regulation of chromatin remodelers:** ncRNAs can regulate the activity of chromatin remodelers, enzymes that alter the position of nucleosomes on DNA. This can affect the accessibility of DNA to transcription factors and other regulatory proteins, ultimately influencing heterochromatin formation.

5. **Inducing DNA methylation:** Some ncRNAs can trigger DNA methylation, a key modification associated with heterochromatin. This can lead to the silencing of genes and the establishment of heterochromatin domains.

The specific ncRNAs involved in heterochromatin formation vary depending on the organism and the specific genomic region being targeted. However, the general mechanisms described above provide a framework for understanding how ncRNAs contribute to this fundamental process.

These mechanisms highlight the crucial role of ncRNAs in regulating gene expression, controlling genome organization, and maintaining genome stability. They also underscore the complexity and versatility of the ncRNA world, showcasing their diverse functions beyond protein coding.'
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Proteins (2)

Compounds (16)