PRDM9

From Wikipedia, the free encyclopedia
Jump to: navigation, search
PRDM9
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases PRDM9, MEISETZ, MSBP3, PFM6, PRMD9, ZNF899, PR domain 9
External IDs MGI: 2384854 HomoloGene: 104139 GeneCards: 56979
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
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 Human View/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[edit]

PRDM9 is thought to mediate the process of meiotic homologous recombination.[5]

Recombination hotspots[edit]

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[edit]

  1. ^ positive-regulatory domain

References[edit]

  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 2794550free to read. PMID 20041164.  open access publication - free to read
  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 3117304free to read. PMID 21460839. 
  6. ^ 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. 
  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 4287450free to read. PMID 25568937. 

Further reading[edit]

External links[edit]

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