Cited by 415Genomics and Chromatin DynamicsChromosomal and Genetic VariationsDNA Repair Mechanisms

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Genetic recombination is directed away from functional genomic elements in mice

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Brick, Kevin, Smagulova, Fatima, Khil, Pavel, Camerini-Otero, R. Daniel, Petukhova, Galina V.·2012·Nature

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Abstract

Genetic recombination occurs during meiosis, the key developmental programme of gametogenesis. Recombination in mammals has been recently linked to the activity of a histone H3 methyltransferase, PR domain containing 9 (PRDM9), the product of the only known speciation-associated gene in mammals. PRDM9 is thought to determine the preferred recombination sites--recombination hotspots--through sequence-specific binding of its highly polymorphic multi-Zn-finger domain. Nevertheless, Prdm9 knockout mice are proficient at initiating recombination. Here we map and analyse the genome-wide distribution of recombination initiation sites in Prdm9 knockout mice and in two mouse strains with different Prdm9 alleles and their F(1) hybrid. We show that PRDM9 determines the positions of practically all hotspots in the mouse genome, with the exception of the pseudo-autosomal region (PAR)--the only area of the genome that undergoes recombination in 100% of cells. Surprisingly, hotspots are still observed in Prdm9 knockout mice, and as in wild type, these hotspots are found at H3 lysine 4 (H3K4) trimethylation marks. However, in the absence of PRDM9, most recombination is initiated at promoters and at other sites of PRDM9-independent H3K4 trimethylation. Such sites are rarely targeted in wild-type mice, indicating an unexpected role of the PRDM9 protein in sequestering the recombination machinery away from gene-promoter regions and other functional genomic elements.

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Authors: Brick, K., Smagulova, F., Khil, P., Camerini-Otero, R. D., & Petukhova, G. V.
Affiliations: National Institute of Diabetes and Digestive and Kidney Diseases (US)
Uniformed Services University of the Health Sciences (US)
National Institutes of Health (US)
Corresponding author: Petukhova, Galina V.
ORCID: Brick, Kevin
Smagulova, Fatima
Khil, Pavel
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2012-05
Volume: 485
Issue: 7400
Pages: 642-645
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature11089
PMC: PMC3367396
OpenAlex: W2024459631
Cited by: 414
References: 30
Citations by year: 2026: 19 · 2025: 15 · 2024: 31 · 2023: 31 · 2022: 30 · 2021: 27 · 2020: 28 · 2019: 31 · 2018: 36 · 2017: 33 · 2016: 36 · 2015: 31 · 2014: 32 · 2013: 24 · 2012: 10
FWCI: 12.48
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
HAL (submittedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: National Institutes of Health
National Institute of General Medical Sciences (R01GM084104)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Keywords: PRDM9, meiotic recombination, recombination hotspots, H3K4 trimethylation, promoter targeting, meiosis
MeSH terms: Alleles, Amino Acid Sequence, Animals, Base Sequence, Histones, Meiosis, Methylation, Molecular Sequence Data, Promoter Regions, Genetic, Histone-Lysine N-Methyltransferase, Recombination, Genetic, Genome, Mice, Knockout, Mice, DNA Breaks, Double-Stranded

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Genetic recombination is directed away from functional genomic elements in mice

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