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H2020Individual fellowship2015–2017

PRDM9Recomb · The Evolution of PRDM9 Binding and Genomic Localization of Meiotic Recombination Events

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2015-05-01 → 2017-04-30
EU contribution
€195,455
Participants
1
Scheme
MSCA-IF-EF-ST

Lines connect the coordinator with its partners.

Results in brief

The Evolution of PRDM9 Binding and Genomic Localization of Meiotic Recombination Events

Meiotic recombination, or genetic recombination, is an essential process for sexually reproducing organisms. The appropriate genomic distribution of recombination events is necessary for the accurate transmission of genetic from one generation to the next. Extensive research has demonstrated that a major determinant of recombination sites in mice and in humans is protein PRDM9. PRDM9 binds to DNA in a sequence-dependent manner, and also catalyses the methylation of histones, which, in addition to altering the recombination landscape, also changes the chromatin architecture at different genomic loci within the germline. Although meiotic recombination is an essential process, it is rapidly evolving, and it's evolution is also linked to the evolution of PRDM9, the chromatin landscape, and the evolution of the genome. The initial hypothesis of the project was that additional factors act in concert with PRDM9 to specify sites of meiotic recombination events. The overall objectives of the project is to understand the interplay between the evolution of the genome, the evolution of meiotic recombination, and the evolution of the chromatin landscape in the germline. Throughout the two-year duration of the fellowship, we have investigated and utilised different techniques to map recombination events in mammals, we have investigated the contribution of retrotransposons to meiotic recombination events, and we have mapped the evolution of the chromatin landscape during meiosis across mammals. These studies are ongoing, and will provide insights into the factors that influence recombination and genome evolution in mammals.

Data: CORDIS, © European Union

Project objective

Meiotic recombination is an essential process for sexually reproducing organisms. The appropriate genomic distribution of recombination events is necessary for the accurate transmission of genetic information from one generation to the next. Extensive research has demonstrated that a major determinant of recombination sites in mice and humans is the DNA-binding protein PRDM9. An intriguing feature of PRDM9 is the exceptionally rapid evolution of its DNA-binding domain, which causes enormous variability in the locations of recombination events, even within a single species. To date, our understanding of PRDM9’s genome-wide distribution is based largely on its predicted DNA-binding specificity, however, the presence of a predicted consensus motif alone is not a strong predictor of recombination locations. Here, I will test the hypothesis that additional factors act in concert with the rapidly evolving PRDM9 protein to specify sites of meiotic recombination events. I will directly map and compare the genome-wide distribution of PRDM9 in different mouse strains to understand the evolution and principles of its binding. I will also pioneer a single-cell based approach that can distinguish between different classes of recombination events to build a high-resolution genome-wide recombination map to further dissect the role of PRDM9, and to identify additional factors, that shape the recombination landscape.

Original text from CORDIS.

Participants

  • THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE · CAMBRIDGECoordinatorUnited Kingdom

Links

Data: CORDIS, © European Union