PRDM9

PRDM9
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
Aliases PRDM9, MEISETZ, MSBP3, PFM6, PRMD9, ZNF899, PR domain 9
External IDs MGI: 2384854 HomoloGene: 104139 GeneCards: PRDM9
Orthologs
Species Human Mouse
Entrez

56979

213389

Ensembl

ENSG00000164256

ENSMUSG00000051977

UniProt

Q9NQV7

Q96EQ9

RefSeq (mRNA)

NM_020227
NM_001310214

NM_144809

RefSeq (protein)

NP_001297143.1
NP_064612.2

n/a

Location (UCSC) Chr 5: 23.44 – 23.53 Mb Chr 17: 15.54 – 15.56 Mb
PubMed search [1] [2]
Wikidata
View/Edit HumanView/Edit Mouse

PR domain[note 1] zinc finger protein 9 is a protein that in humans is encoded by the Prdm9 gene.[3] The protein has histone H3K4 trimethyltransferase activity, a KRAB domain, and a DNA-binding domain consisting of multiple tandem C2H2 zinc finger (ZF) domains.[4] 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.[5]

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.[6] There are approximately 30,000 to 50,000 hotspots within the human genome corresponding to one for every 50-100kb DNA on average.[6] 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.[6] These hotspots are predicted binding sites for PRDM9 protein.[7]

PRDM9 is a meiosis specific histone methyltransferase and, upon binding to DNA, it catalyzes trimethylation of histone H3 at lysine 4.[8] As a result, local nucleosomes are reorganized. This reorganization is apparently associated with increased probability of recombination.

Notes

  1. ↑ positive-regulatory domain

References

  1. ↑ "Human PubMed Reference:".
  2. ↑ "Mouse PubMed Reference:".
  3. ↑ "Entrez Gene: PR domain containing 9".
  4. ↑ 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 2794550Freely accessible. PMID 20041164.
  5. ↑ 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 3117304Freely accessible. PMID 21460839.
  6. 1 2 3 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.
  7. ↑ de Massy B (2014). "Human genetics. Hidden features of human hotspots". Science. 346 (6211): 808–9. doi:10.1126/science.aaa0612. PMID 25395519.
  8. ↑ 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 4287450Freely accessible. PMID 25568937.

Further reading

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


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