Publication Date:
2012-06-05
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367396/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367396/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brick, Kevin -- Smagulova, Fatima -- Khil, Pavel -- Camerini-Otero, R Daniel -- Petukhova, Galina V -- 1R01GM084104-01A1/GM/NIGMS NIH HHS/ -- R01 GM084104/GM/NIGMS NIH HHS/ -- R01 GM084104-01A1/GM/NIGMS NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2012 May 13;485(7400):642-5. doi: 10.1038/nature11089.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, Maryland 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22660327" target="_blank"〉PubMed〈/a〉
Keywords:
Alleles
;
Amino Acid Sequence
;
Animals
;
Base Sequence
;
*DNA Breaks, Double-Stranded
;
Genome/*genetics
;
Histone-Lysine N-Methyltransferase/deficiency/genetics/*metabolism
;
Histones/chemistry/metabolism
;
Meiosis/genetics
;
Methylation
;
Mice
;
Mice, Knockout
;
Molecular Sequence Data
;
Promoter Regions, Genetic/*genetics
;
Recombination, Genetic/*genetics
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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