retrotransposon silencing by heterochromatin formation

Definition

Target type: biologicalprocess

A retrotransposon silencing mechanism involving heterochromatin assembly. Heterochromatin is a chromatin conformation that is refractory to transcription. [PMID:25247314, PMID:28951459, PMID:32823517]

Retrotransposons are mobile genetic elements that can replicate and insert themselves into new locations within a genome. Their uncontrolled activity can disrupt gene function and lead to genomic instability. To prevent this, eukaryotic cells have evolved sophisticated mechanisms to silence retrotransposons, one of which is heterochromatin formation. Heterochromatin is a highly condensed form of chromatin that is characterized by its repressive nature and the presence of specific histone modifications. The process of retrotransposon silencing by heterochromatin formation can be summarized as follows:

1. **Recognition of retrotransposon sequences:** Specialized proteins, such as PIWI proteins and small RNA molecules (siRNAs and piRNAs), recognize specific sequences within retrotransposon DNA or RNA. These proteins bind to the retrotransposon elements and serve as markers for heterochromatin formation.
2. **Recruitment of histone-modifying enzymes:** Once bound to the retrotransposon, the recognition proteins recruit histone-modifying enzymes, such as histone methyltransferases (HMTs) and histone deacetylases (HDACs). These enzymes catalyze specific modifications on histone proteins, leading to the formation of heterochromatin.
3. **Histone modifications:** HMTs deposit methyl groups on histone tails, specifically on lysine residues. In particular, methylation of histone H3 at lysine 9 (H3K9me) and methylation of histone H3 at lysine 27 (H3K27me) are key modifications associated with heterochromatin formation. HDACs remove acetyl groups from histone tails, which promotes compaction of chromatin and gene silencing.
4. **Heterochromatin formation:** The combination of histone modifications, including methylation and deacetylation, leads to the formation of heterochromatin. This highly condensed chromatin structure hinders the access of transcription factors and other regulatory proteins to retrotransposon DNA, effectively silencing their transcription.
5. **Spread of heterochromatin:** The heterochromatin domain can spread along the chromosome, silencing not only the initial retrotransposon but also neighboring genomic regions. This spread is mediated by specialized proteins, such as HP1, which bind to specific histone modifications and recruit additional histone-modifying enzymes.
6. **Maintenance of silencing:** The silenced state is maintained through the ongoing activity of histone-modifying enzymes and the presence of heterochromatin-associated proteins. This ensures that retrotransposons remain silenced over time and across generations.

Overall, retrotransposon silencing by heterochromatin formation is a crucial process that protects genome integrity and ensures proper gene expression. This complex mechanism involves a delicate interplay of DNA recognition, histone modifications, and chromatin structure, all working together to prevent the uncontrolled activity of mobile genetic elements.'
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Proteins (2)

Compounds (8)