PRDM9

PR domain containing 9
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 4IJD​
Identifiers
Symbols	PRDM9 ; MEISETZ; MSBP3; PFM6; ZNF899
External IDs	OMIM: 609760 MGI: 2384854 HomoloGene: 104139 GeneCards: PRDM9 Gene
EC number	2.1.1.43
Gene ontology Molecular function • nucleic acid binding • histone-lysine N-methyltransferase activity • metal ion binding Cellular component • nucleoplasm • chromosome Biological process • meiotic gene conversion • chromatin organization • transcription, DNA-templated • regulation of transcription, DNA-templated • positive regulation of reciprocal meiotic recombination • histone lysine methylation Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	56979	213389
Ensembl	ENSG00000164256	ENSMUSG00000051977
UniProt	Q9NQV7	Q96EQ9
RefSeq (mRNA)	NM_001310214	NM_144809
RefSeq (protein)	NP_001297143	NP_659058
Location (UCSC)	Chr 5: 23.51 – 23.53 Mb	Chr 17: 15.54 – 15.56 Mb
PubMed search

PR domain^{[note 1]} zinc finger protein 9 is a protein that in humans is encoded by the Prdm9 gene.^[1] The protein has histone H3K4 trimethyltransferase activity, a KRAB domain, and a DNA-binding domain consisting of multiple tandem C2H2 zinc finger (ZF) domains.^[2] PRDM9 specifically trimethylates lysine 4 of histone H3 during meiotic prophase and is essential for proper meiotic progression, but does not have the ability to mono- and dimethylate lysine 4 of histone H3. H3K4 methylation represents a specific tag for epigenetic transcriptional activation which plays a central role in the transcriptional activation of genes during early meiotic prophase.

Function

PRDM9 is thought to mediate the process of meiotic homologous recombination.^[3]

Recombination hotspots

In humans and mice, recombination occurs at elevated rates at particular sites along the chromosomes called recombination hotspots. Hotspots are regions of DNA about 1-2kb in length.^[4] There are approximately 30,000 to 50,000 hotspots within the human genome corresponding to one for every 50-100kb DNA on average.^[4] In humans, the average number of crossover recombination events per hotspot is one per 1,300 meioses, and the most extreme hotspot has a crossover frequency of one per 110 meioses.^[4] These hotspots are predicted binding sites for PRDM9 protein.^[5]

PRDM9 is a meiosis specific histone methyltransferase and, upon binding to DNA, it catalyzes trimethylation of histone H3 at lysine 4.^[6] As a result, local nucleosomes are reorganized. This reorganization is apparently associated with increased probability of recombination.

Notes

1. positive-regulatory domain

References

1. "Entrez Gene: PR domain containing 9".
2. Thomas JH, Emerson RO, Shendure J (2009). "Extraordinary molecular evolution in the PRDM9 fertility gene". PLoS ONE 4 (12): e8505. doi:10.1371/journal.pone.0008505. PMC 2794550. PMID 20041164.
3. Smagulova F, Gregoretti IV, Brick K, Khil P, Camerini-Otero RD, Petukhova GV (April 2011). "Genome-wide analysis reveals novel molecular features of mouse recombination hotspots". Nature 472 (7343): 375–8. doi:10.1038/nature09869. PMC 3117304. PMID 21460839.
4. Myers S, Spencer CC, Auton A, Bottolo L, Freeman C, Donnelly P, McVean G (2006). "The distribution and causes of meiotic recombination in the human genome". Biochem. Soc. Trans. 34 (Pt 4): 526–30. doi:10.1042/BST0340526. PMID 16856851.
5. de Massy B (2014). "Human genetics. Hidden features of human hotspots". Science 346 (6211): 808–9. doi:10.1126/science.aaa0612. PMID 25395519.
6. Baker CL, Kajita S, Walker M, Saxl RL, Raghupathy N, Choi K, Petkov PM, Paigen K (2015). "PRDM9 drives evolutionary erosion of hotspots in Mus musculus through haplotype-specific initiation of meiotic recombination". PLoS Genet. 11 (1): e1004916. doi:10.1371/journal.pgen.1004916. PMC 4287450. PMID 25568937.

Further reading

• Baudat F, Buard J, Grey C, et al. (2010). "PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice.". Science 327 (5967): 836–40. doi:10.1126/science.1183439. PMID 20044539.
• Berg IL, Neumann R, Lam KW, et al. (2010). "PRDM9 variation strongly influences recombination hot-spot activity and meiotic instability in humans.". Nat. Genet. 42 (10): 859–63. doi:10.1038/ng.658. PMC 3092422. PMID 20818382.
• Irie S, Tsujimura A, Miyagawa Y, et al. (2009). "Single-nucleotide polymorphisms of the PRDM9 (MEISETZ) gene in patients with nonobstructive azoospermia.". J. Androl. 30 (4): 426–31. doi:10.2164/jandrol.108.006262. PMID 19168450.
• Sun XJ, Xu PF, Zhou T, et al. (2008). "Genome-wide survey and developmental expression mapping of zebrafish SET domain-containing genes.". PLoS ONE 3 (1): e1499. doi:10.1371/journal.pone.0001499. PMC 2200798. PMID 18231586.
• Xiao B, Wilson JR, Gamblin SJ (2003). "SET domains and histone methylation.". Curr. Opin. Struct. Biol. 13 (6): 699–705. doi:10.1016/j.sbi.2003.10.003. PMID 14675547.
• Wahls WP, Swenson G, Moore PD (1991). "Two hypervariable minisatellite DNA binding proteins.". Nucleic Acids Res. 19 (12): 3269–74. doi:10.1093/nar/19.12.3269. PMC 328321. PMID 2062643.
• Jiang GL, Huang S (2000). "The yin-yang of PR-domain family genes in tumorigenesis.". Histol. Histopathol. 15 (1): 109–17. PMID 10668202.
• Parvanov ED, Petkov PM, Paigen K (2010). "Prdm9 controls activation of mammalian recombination hotspots.". Science 327 (5967): 835. doi:10.1126/science.1181495. PMC 2821451. PMID 20044538.
• Myers S, Bowden R, Tumian A, et al. (2010). "Drive against hotspot motifs in primates implicates the PRDM9 gene in meiotic recombination.". Science 327 (5967): 876–9. doi:10.1126/science.1182363. PMID 20044541.
• Miyamoto T, Koh E, Sakugawa N, et al. (2008). "Two single nucleotide polymorphisms in PRDM9 (MEISETZ) gene may be a genetic risk factor for Japanese patients with azoospermia by meiotic arrest.". J. Assist. Reprod. Genet. 25 (11-12): 553–7. doi:10.1007/s10815-008-9270-x. PMC 2593767. PMID 18941885.
• Hussin J, Sinnett D, Casals F, et al. (2013). "Rare allelic forms of PRDM9 associated with childhood leukemogenesis.". Genome Res. 23 (3): 419–30. doi:10.1101/gr.144188.112. PMID 23222848.

External links

• PRDM9 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
• UCSC GenomeWiki - PRDM9: Meiosis and Recombination

This article incorporates text from the United States National Library of Medicine, which is in the public domain.