Journal
SCIENCE
Volume 327, Issue 5967, Pages 836-840Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1183439
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Funding
- CNRS
- Association pour la Recherche sur le Cancer [ARC 3939]
- Fondation Jer me Lejeune
- Agence Nationale de la Recherche [ANR-06-BLAN-0160-01, ANR-09-BLAN-0269-01]
- Electricite de France
- NIH [HD21244, HL085197, GM83098]
- American Recovery and Reinvestment Act [03S1]
- Howard Hughes Medical Institute
- Agence Nationale de la Recherche (ANR) [ANR-06-BLAN-0160] Funding Source: Agence Nationale de la Recherche (ANR)
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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.
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