Anatomy of mouse recombination hot spots

Genome-wide analyses have suggested thousands of meiotic recombination hot spots across mammalian genomes. However, very few hot spots have been directly analyzed at a sub-kb scale for crossover (CO) activity. Using recombinant inbred strains as a CO library, here we report the identification and detailed characterization of seven new meiotic hot spots on mouse chromosome 19, more than doubling the number of currently available mouse hot spots. Although a shared feature is the narrow 1.5–2.5-kb width of these recombinogenic sites, these analyses revealed that hot spots have diverse sequence attributes and distinct symmetric and asymmetric CO profiles. Interestingly, CO molecules with discontinuous conversion tracts are commonly observed, contrasting with those found in human. Furthermore, unlike human hot spots, those present in the mouse do not necessarily have a quasi-normal CO distribution but harbor CO repulsion zones within recombinogenic cores. We propose a model where local chromatin landscape directs these repulsion zones

Foxn1[Cre] Expression in the Male Germline.

Foxn1 (forkhead box N1), also known as the nude gene or winged-helix nude (Whn), is a forkhead transcription factor thought to be restricted to keratinocytes in the skin and thymus. Consistent with this tissue distribution, spontaneous or targeted mutation of Foxn1 results in the absence of both hair and a thymus. Genetic manipulation of the Foxn1 locus thus represents a powerful tool for tissue specific gene control in the skin and thymus, and tools such as Cre recombinase under control of the Foxn1 locus are widely used for this purpose. Unexpectedly, we show that Foxn1[Cre] exhibits unexpected activity in male germ cells, resulting in ubiquitous targeting of loxP-flanked alleles in all tissues in offspring from Foxn1[Cre] expressing male mice. Inheritance of recombined loxP alleles occurs independently of Cre inheritance (i.e., offspring lacking Cre nonetheless exhibit recombined alleles), suggesting that Foxn1[Cre] induced recombination in male germ cells must occur prior to meiosis in diploid germ cells. Together with previously published data, our results show that Foxn1, and alleles under its control, are expressed in the pre-meiotic male germline, revealing a new tool for germline targeting of genes, and raising important concerns for gender selection when using Foxn1 regulatory elements

A Global Expression Switch Marks Pachytene Initiation during Mouse Male Meiosis

Male spermatogenesis is an essential and complex process necessary to gain totipotency and allow a whole new organism to develop upon fertilization. While single-gene based studies have provided insights into the mechanisms underlying spermatogenesis, detailed global profiling of all the key meiotic stages is required to fully define these processes. Here, by isolating highly enriched mouse meiotic cell populations, we have generated a comprehensive gene expression atlas of mammalian meiosis. Our data define unique signatures for the specific stages of meiosis, including global chromosome X inactivation and reactivation. The data also reveal profound switches in global gene expression at the initiation of pachynema that are reminiscent of the commitment to meiosis observed in budding yeast. Overall, this meiotic atlas provides an exhaustive blueprint and resource for mammalian gametogenesis and meiosis

A Global Expression Switch Marks Pachytene Initiation during Mouse Male Meiosis

Male spermatogenesis is an essential and complex process necessary to gain totipotency and allow a whole new organism to develop upon fertilization. While single-gene based studies have provided insights into the mechanisms underlying spermatogenesis, detailed global profiling of all the key meiotic stages is required to fully define these processes. Here, by isolating highly enriched mouse meiotic cell populations, we have generated a comprehensive gene expression atlas of mammalian meiosis. Our data define unique signatures for the specific stages of meiosis, including global chromosome X inactivation and reactivation. The data also reveal profound switches in global gene expression at the initiation of pachynema that are reminiscent of the commitment to meiosis observed in budding yeast. Overall, this meiotic atlas provides an exhaustive blueprint and resource for mammalian gametogenesis and meiosis

Inappropriate reporter activity, independent of Cre expression, in offspring from Cre+ male, but not female, mice.

<p>a) a conditional Gfp reporter expression in white blood cells (WBC) from Cre+ or Cre- offspring of Cre+ male or female parents (x B6 cross). WBC are uniformly Gfp+ when the male parent was Cre+, regardless of whether the offspring inherited Cre. Expression of a Foxn1[Cre]-activated conditional reporter is not expected in WBC from either Cre+ or Cre- offspring, since Foxn1 is not expressed in blood cells, as is the case when Foxn1[Cre] was carried by the mother. b) a summary of larger numbers of offspring from multiple independent litters.</p