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.
Publication types
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Research Support, American Recovery and Reinvestment Act
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Alleles
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Amino Acid Sequence
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Animals
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Base Sequence
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Binding Sites
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DNA / chemistry
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DNA / metabolism
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DNA Breaks, Double-Stranded
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Genome
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Genome, Human
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Genotype
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Histone-Lysine N-Methyltransferase / chemistry
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Histone-Lysine N-Methyltransferase / genetics*
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Histone-Lysine N-Methyltransferase / metabolism*
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Humans
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Meiosis / genetics*
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Mice
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Mice, Inbred C57BL
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Molecular Sequence Data
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Phenotype
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Recombination, Genetic*
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Zinc Fingers / genetics
Substances
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DNA-Binding Proteins
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DNA
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Histone-Lysine N-Methyltransferase
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PRDM9 protein, human
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prdm9 protein, mouse
Associated data
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GENBANK/GU216222
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GENBANK/GU216223
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GENBANK/GU216224
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GENBANK/GU216225
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GENBANK/GU216226
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GENBANK/GU216227
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GENBANK/GU216228
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GENBANK/GU216229
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GENBANK/GU216230