PRDM9
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
- ^ positive-regulatory domain
References
- ^ "Entrez Gene: PR domain containing 9".
- ^ 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
- ^ 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ a b c 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.
- ^ de Massy B (2014). "Human genetics. Hidden features of human hotspots". Science. 346 (6211): 808–9. doi:10.1126/science.aaa0612. PMID 25395519.
- ^ 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.
{{cite journal}}: CS1 maint: unflagged free DOI (link)
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.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - 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 U.S. 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.
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