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PMID: 20044539 Published · ppublish English Journal Article Research Support, American Recovery and Reinvestment Act Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice.

Science (New York, N.Y.) ·Vol. 327 ·No. 5967 ·2010-02-12 ·Pages 836-40

Baudat F, Buard J, Grey C, Fledel-Alon A, Ober C, Przeworski M, Coop G, de Massy B

Abstract

Meiotic recombination events cluster into narrow segments of the genome, defined as hotspots. Here, we demonstrate that a major player for hotspot specification is the Prdm9 gene. First, two mouse strains that differ in hotspot usage are polymorphic for the zinc finger DNA binding array of PRDM9. Second, the human consensus PRDM9 allele is predicted to recognize the 13-mer motif enriched at human hotspots; this DNA binding specificity is verified by in vitro studies. Third, allelic variants of PRDM9 zinc fingers are significantly associated with variability in genome-wide hotspot usage among humans. Our results provide a molecular basis for the distribution of meiotic recombination in mammals, in which the binding of PRDM9 to specific DNA sequences targets the initiation of recombination at specific locations in the genome.

MeSH Terms
Alleles Amino Acid Sequence Animals Base Sequence Binding Sites DNA/chemistry,metabolism DNA Breaks, Double-Stranded DNA-Binding Proteins/chemistry,genetics,metabolism Genome Genome, Human Genotype Histone-Lysine N-Methyltransferase/chemistry,genetics,metabolism Humans Meiosis/genetics Mice Mice, Inbred C57BL Molecular Sequence Data Phenotype Recombination, Genetic Zinc Fingers/genetics
Chemicals
DNA-Binding Proteins DNA Histone-Lysine N-Methyltransferase PRDM9 protein, human prdm9 protein, mouse
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Baudat F
Institut de Génétique Humaine, UPR1142, CNRS, Montpellier, France.
Buard J
Grey C
Fledel-Alon A
Ober C
Przeworski M
Coop G
de Massy B
References (28)
28 references, click to expand
  1. Fine-scale recombination patterns differ between chimpanzees and humans.
    Nat Genet. 2005 Apr;37(4):429-34 PMID: 15723063
  2. A fine-scale map of recombination rates and hotspots across the human genome.
    Science. 2005 Oct 14;310(5746):321-4 PMID: 16224025
  3. Trans-regulation of mouse meiotic recombination hotspots by Rcr1.
    PLoS Biol. 2009 Feb 17;7(2):e36 PMID: 19226189
  4. Histone H3 lysine 4 trimethylation marks meiotic recombination initiation sites.
    EMBO J. 2009 Jan 21;28(2):99-111 PMID: 19078966
  5. Accelerated evolution of the Prdm9 speciation gene across diverse metazoan taxa.
    PLoS Genet. 2009 Dec;5(12):e1000753 PMID: 19997497
  6. Zinc Finger Database (ZiFDB): a repository for information on C2H2 zinc fingers and engineered zinc-finger arrays.
    Nucleic Acids Res. 2009 Jan;37(Database issue):D279-83 PMID: 18812396
  7. A common sequence motif associated with recombination hot spots and genome instability in humans.
    Nat Genet. 2008 Sep;40(9):1124-9 PMID: 19165926
  8. The fine-scale structure of recombination rate variation in the human genome.
    Science. 2004 Apr 23;304(5670):581-4 PMID: 15105499
  9. Distribution of meiotic recombination sites.
    Trends Genet. 2003 Sep;19(9):514-22 PMID: 12957545
  10. Design and selection of novel Cys2His2 zinc finger proteins.
    Annu Rev Biochem. 2001;70:313-40 PMID: 11395410
  11. A mouse speciation gene encodes a meiotic histone H3 methyltransferase.
    Science. 2009 Jan 16;323(5912):373-5 PMID: 19074312
  12. Factors influencing recombination frequency and distribution in a human meiotic crossover hotspot.
    Hum Mol Genet. 2005 Aug 1;14(15):2277-87 PMID: 15987698
  13. Mammalian meiotic recombination hot spots.
    Annu Rev Genet. 2007;41:369-99 PMID: 18076329
  14. High-resolution mapping of crossovers reveals extensive variation in fine-scale recombination patterns among humans.
    Science. 2008 Mar 7;319(5868):1395-8 PMID: 18239090
  15. An evolutionary view of human recombination.
    Nat Rev Genet. 2007 Jan;8(1):23-34 PMID: 17146469
  16. The hotspot conversion paradox and the evolution of meiotic recombination.
    Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8058-63 PMID: 9223314
  17. The recombinational anatomy of a mouse chromosome.
    PLoS Genet. 2008 Jul 11;4(7):e1000119 PMID: 18617997
  18. Comparison of fine-scale recombination rates in humans and chimpanzees.
    Science. 2005 Apr 1;308(5718):107-11 PMID: 15705809
  19. Intensely punctate meiotic recombination in the class II region of the major histocompatibility complex.
    Nat Genet. 2001 Oct;29(2):217-22 PMID: 11586303
  20. Reciprocal crossover asymmetry and meiotic drive in a human recombination hot spot.
    Nat Genet. 2002 Jul;31(3):267-71 PMID: 12089523
  21. Playing hide and seek with mammalian meiotic crossover hotspots.
    Trends Genet. 2007 Jun;23(6):301-9 PMID: 17434233
  22. Un ménage à quatre: the molecular biology of chromosome segregation in meiosis.
    Cell. 2003 Feb 21;112(4):423-40 PMID: 12600308
  23. Genome-wide control of the distribution of meiotic recombination.
    PLoS Biol. 2009 Feb 17;7(2):e35 PMID: 19226188
  24. A histone H3 methyltransferase controls epigenetic events required for meiotic prophase.
    Nature. 2005 Nov 17;438(7066):374-8 PMID: 16292313
  25. Distinct histone modifications define initiation and repair of meiotic recombination in the mouse.
    EMBO J. 2009 Sep 2;28(17):2616-24 PMID: 19644444
  26. Unexpected failure rates for modular assembly of engineered zinc fingers.
    Nat Methods. 2008 May;5(5):374-5 PMID: 18446154
  27. Beyond the "recognition code": structures of two Cys2His2 zinc finger/TATA box complexes.
    Structure. 2001 Aug;9(8):717-23 PMID: 11587646
  28. Spo11 and the Formation of DNA Double-Strand Breaks in Meiosis.
    Genome Dyn Stab. 2008 Jan 1;2:81-123 PMID: 21927624
Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1183439
Published
2010-02-12
Epub
2009-00-31
Pages
836-40
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC4295902
Subset
IM
Grants
NIGMS NIH HHS · GM83098 · United States
NICHD NIH HHS · HD21244 · United States
NHLBI NIH HHS · HL085197 · United States
Howard Hughes Medical Institute · United States
NHLBI NIH HHS · R01 HL085197 · United States
NICHD NIH HHS · R01 HD021244 · United States
PHS HHS · 03S1 · United States
NIGMS NIH HHS · R01 GM083098 · United States
Databases
GENBANK
GU216222, GU216223, GU216224, GU216225, GU216226, GU216227, GU216228, GU216229, GU216230
Corrections
ErratumIn
-
CommentIn
PMID: 20150474
CommentIn
PMID: 20210982
External Links
PubMed source DOI: 10.1126/science.1183439 PMC Full Text View journal details
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