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Generation of Genetically Modified Mice through the Microinjection of Oocytes
Published on: June 15, 2017
Genetic recombination is directed away from functional genomic elements in mice
Kevin Brick1, Fatima Smagulova, Pavel Khil
1National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, Maryland 20892, USA.
Nature
|June 5, 2012
Summary
The PRDM9 protein typically directs genetic recombination to specific hotspots. In its absence, recombination still occurs but is rerouted to gene promoters and other genomic sites.
Area of Science:
- Genetics
- Molecular Biology
- Reproductive Biology
Background:
- Genetic recombination during meiosis is crucial for gametogenesis and speciation.
- PR domain containing 9 (PRDM9) is a histone methyltransferase linked to mammalian recombination and speciation.
- PRDM9's zinc-finger domain is believed to specify recombination hotspots through sequence-specific binding.
Purpose of the Study:
- To map and analyze the genome-wide distribution of recombination initiation sites in Prdm9 knockout mice and different mouse strains.
- To elucidate the role of PRDM9 in determining recombination hotspot locations.
- To understand the mechanisms of PRDM9-independent recombination.
Main Methods:
- Genome-wide mapping of recombination initiation sites.
- Analysis of recombination patterns in Prdm9 knockout mice, wild-type mice with different alleles, and F(1) hybrids.
- Investigation of histone modifications, specifically H3K4 trimethylation, at recombination sites.
Main Results:
- PRDM9 dictates the location of nearly all mammalian recombination hotspots, except in the pseudo-autosomal region (PAR).
- Recombination hotspots persist in Prdm9 knockout mice, localized at H3K4 trimethylation marks.
- In the absence of PRDM9, recombination predominantly initiates at promoters and other PRDM9-independent H3K4 trimethylation sites.
Conclusions:
- PRDM9 is the primary determinant of recombination hotspot positions in the mouse genome.
- PRDM9 plays an unexpected role in preventing recombination at gene promoters and functional genomic elements.
- The study reveals a novel function of PRDM9 in guiding recombination away from essential regulatory regions.
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