Transvection effects involving DNA methylation during meiosis in the mouse.
High efficiencies of recombination between LoxP elements were initially recorded when the Cre recombinase was expressed in meiotic spermatocytes. However, it was unexpectedly found that LoxP recombination fell to very low values at the second generation of mice expressing Cre during meiosis. The inability of the LoxP elements to serve as recombination substrates was correlated with cytosine methylation, initially in LoxP and transgene sequences, but later extending for distances of at least several kilobases into chromosomal sequences. It also affected the allelic locus, implying a transfer of structural information between alleles similar to the transvection phenomenon described in Drosophila. Once initiated following Cre-LoxP interaction, neither cis-extension nor transvection of the methylated state required the continuous expression of Cre, as they occurred both in germinal and somatic cells and in the fraction of the offspring that had not inherited the Sycp1-Cre transgene. Therefore, these processes depend on a physiological mechanism of establishment and extension of an epigenetic state, for which they provide an experimental model.
Rassoulzadegan
Minoo
M
Unité 470, Institut National de la Santé et de la Recherche Médicale, Université de Nice-Sophia Antipolis, Nice, France.
Magliano
Marc
M
Cuzin
François
F
D000818:Animals; D001483:Base Sequence; D019175:DNA Methylation; D019426:Integrases / Q000235:genetics; D008297:Male; D008540:Meiosis / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D014764:Viral Proteins / Q000235:genetics
D014764:Viral Proteins; C045073:Cre recombinase; D019426:Integrases