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PMID: 19226189 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Trans-regulation of mouse meiotic recombination hotspots by Rcr1.

PLoS biology ·Vol. 7 ·No. 2 ·2009-02-17 ·Pages e36

Parvanov ED, Ng SH, Petkov PM, Paigen K

Abstract

Meiotic recombination is required for the orderly segregation of chromosomes during meiosis and for providing genetic diversity among offspring. Among mammals, as well as yeast and higher plants, recombination preferentially occurs at highly delimited chromosomal sites 1-2 kb long known as hotspots. Although considerable progress has been made in understanding the roles various proteins play in carrying out the molecular events of the recombination process, relatively little is understood about the factors controlling the location and relative activity of mammalian recombination hotspots. To search for trans-acting factors controlling the positioning of recombination events, we compared the locations of crossovers arising in an 8-Mb segment of a 100-Mb region of mouse Chromosome 1 (Chr 1) when the longer region was heterozygous C57BL/6J (B6) x CAST/EiJ (CAST) and the remainder of the genome was either similarly heterozygous or entirely homozygous B6. The lack of CAST alleles in the remainder of the genome resulted in profound changes in hotspot activity in both females and males. Recombination activity was lost at several hotspots; new, previously undetected hotspots appeared; and still other hotspots remained unaffected, indicating the presence of distant trans-acting gene(s) whose CAST allele(s) activate or suppress the activity of specific hotspots. Testing the activity of three activated hotspots in sperm samples from individual male progeny of two genetic crosses, we identified a single trans-acting regulator of hotspot activity, designated Rcr1, that is located in a 5.30-Mb interval (11.74-17.04 Mb) on Chr 17. Using an Escherichia coli cloning assay to characterize the molecular products of recombination at two of these hotspots, we found that Rcr1 controls the appearance of both crossover and noncrossover gene conversion events, indicating that it likely controls the sites of the double-strand DNA breaks that initiate the recombination process.

MeSH Terms
Animals Chromosome Mapping Chromosomes, Mammalian/genetics Crosses, Genetic Crossing Over, Genetic/genetics DNA Breaks, Double-Stranded Gene Conversion Gene Expression Regulation Genome Heterozygote Male Meiosis/genetics Membrane Proteins/genetics Mice Mice, Inbred C57BL Recombination, Genetic Spermatozoa/physiology
Chemicals
Membrane Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Parvanov Emil D
Center for Genome Dynamics, The Jackson Laboratory, Bar Harbor, Maine, USA.
Ng Siemon H S
Petkov Petko M
Paigen Kenneth
Conflict of Interest

Competing interests. The authors have declared that no competing interests exist.

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Article Info
Journal
PLoS biology
Abbr.
PLoS Biol
ISSN
1545-7885
DOI
10.1371/journal.pbio.1000036
Published
2009-02-17
Pages
e36
Language
English
Region
United States
NLM ID
101183755
PMCID
PMC2642880
Subset
IM
Grants
NIGMS NIH HHS · R01 GM078452 · United States
NIGMS NIH HHS · R01 GM078643 · United States
NCI NIH HHS · P30 CA034196 · United States
NCI NIH HHS · CA34196 · United States
NIGMS NIH HHS · P50 GM076468 · United States
External Links
PubMed source DOI: 10.1371/journal.pbio.1000036 PMC Full Text View journal details
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