PRDM9, a driver of the genetic map in vertebrates

Orateur : Corinne GREY (IGH, Montpellier)

During meiosis, maternal and paternal chromosomes undergo exchanges by homologous recombination (crossing overs). This is essential for fertility and contributes to genome evolution. In most eukaryotes, sites of meiotic recombination, also called hotspots, follow a distinct pattern in the genome called genetic map. These sites are generally regions of accessible chromatin, but in many vertebrates, they are specified by the PRDM9 histone methyl transferase. PRDM9 triggers site-specific recombination activity by acting on three levels : specific DNA binding, methylation of histones in surrounding nucleosomes and interaction with proteins. This in turn trigger conformational changes in the chromosome, leading to the recruitment of the meiotic double strand break machinery. Surprisingly, the repair of meiotic double strand breaks by homologous recombination leads over time to the erosion of hotspot sequences, and thus to the loss of their potential to be broken. Interestingly, the rapid evolution of the PRDM9 DNA binding domain, allows maintaining a sufficient number of active hotspots in the genome over time. Here I will present an overview of the history of the discovery of PRDM9 as a factor specifying the genetic map in mammals, and show you our latest results concerning the in vivo binding of PRDM9, revealing new interesting insights in a potential role of PRDM9 in local changes of the conformation of meiotic chromosomes.

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