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PRDM9

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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.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) Open access icon
  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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ 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.
  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.{{cite journal}}: CS1 maint: unflagged free DOI (link)

Further reading

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