PRDM9

PRDM9_Domain_Architecture.png

PRDM9 is a gene that encodes a protein known as PR domain zinc finger protein 9. This protein plays a crucial role in meiotic recombination, a process essential for the proper segregation of chromosomes during meiosis.

Function

PRDM9 is a histone methyltransferase that specifically trimethylates histone H3 at lysine 4 (H3K4me3). This modification is associated with the activation of meiotic recombination hotspots, regions in the genome where genetic recombination occurs more frequently. PRDM9 binds to specific DNA sequences at these hotspots and facilitates the formation of double-strand breaks (DSBs), which are necessary for the exchange of genetic material between homologous chromosomes.

Structure

The PRDM9 protein contains several important domains:

• A PR/SET domain, which is responsible for its histone methyltransferase activity.
• Multiple zinc finger domains, which enable the protein to bind to specific DNA sequences.
• A KRAB domain, which is involved in transcriptional repression.

Genetic Variation

PRDM9 is highly polymorphic, meaning that there is a significant amount of variation in the DNA sequence of this gene among different individuals. This polymorphism affects the binding specificity of PRDM9 to DNA and, consequently, the location of meiotic recombination hotspots. Variations in PRDM9 have been linked to differences in fertility and the risk of certain genetic disorders.

Clinical Significance

Mutations in PRDM9 have been associated with infertility in both males and females. In particular, certain variants of PRDM9 are linked to azoospermia, a condition characterized by the absence of sperm in the ejaculate. Additionally, PRDM9 has been implicated in genomic disorders that result from abnormal recombination events, such as chromosomal translocations and aneuploidy.

Research

Ongoing research is focused on understanding the precise mechanisms by which PRDM9 regulates meiotic recombination and its broader implications for genome evolution and human health. Studies are also exploring the potential for targeting PRDM9 in therapeutic interventions for infertility and other genetic conditions.

See Also

• Meiosis
• Histone methylation
• Genetic recombination
• Infertility
• Zinc finger