Publication Date:
2011-04-05
Description:
Meiotic recombination predominantly occurs at discrete genomic loci called recombination hotspots, but the features defining these areas are still largely unknown (reviewed in refs 1-5). To allow a comprehensive analysis of hotspot-associated DNA and chromatin characteristics, we developed a direct molecular approach for mapping meiotic DNA double-strand breaks that initiate recombination. Here we present the genome-wide distribution of recombination initiation sites in the mouse genome. Hotspot centres are mapped with approximately 200-nucleotide precision, which allows analysis of the fine structural details of the preferred recombination sites. We determine that hotspots share a centrally distributed consensus motif, possess a nucleotide skew that changes polarity at the centres of hotspots and have an intrinsic preference to be occupied by a nucleosome. Furthermore, we find that the vast majority of recombination initiation sites in mouse males are associated with testis-specific trimethylation of lysine 4 on histone H3 that is distinct from histone H3 lysine 4 trimethylation marks associated with transcription. The recombination map presented here has been derived from a homogeneous mouse population with a defined genetic background and therefore lends itself to extensive future experimental exploration. We note that the mapping technique developed here does not depend on the availability of genetic markers and hence can be easily adapted to other species with complex genomes. Our findings uncover several fundamental features of mammalian recombination hotspots and underline the power of the new recombination map for future studies of genetic recombination, genome stability and evolution.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3117304/" 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/PMC3117304/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smagulova, Fatima -- Gregoretti, Ivan V -- Brick, Kevin -- 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. 2011 Apr 21;472(7343):375-8. doi: 10.1038/nature09869. Epub 2011 Apr 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21460839" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Chromosome Mapping/*methods
;
Chromosome Segregation
;
Chromosomes, Mammalian/*genetics
;
Consensus Sequence
;
Crossing Over, Genetic/genetics
;
*DNA Breaks, Double-Stranded
;
Genetic Markers
;
Genome/*genetics
;
Genomics
;
Histones/metabolism
;
Lysine/metabolism
;
Male
;
Meiosis/*genetics
;
Methylation
;
Mice
;
Mice, Inbred C57BL
;
Molecular Sequence Data
;
Nucleosomes/genetics/metabolism
;
Organ Specificity
;
Recombination, Genetic/*genetics
;
Sister Chromatid Exchange/genetics
;
Testis/metabolism
;
Transcription, 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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