Transposon regulation upon dynamic loss of DNA methylation Marius Walter To cite this version: Marius Walter. Transposon regulation upon dynamic loss of DNA methylation. Development Biology. Université Pierre et Marie Curie - Paris VI, 2015. English. NNT : 2015PA066672. tel-01375673 HAL Id: tel-01375673 https://tel.archives-ouvertes.fr/tel-01375673 Submitted on 3 Oct 2016 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Université Pierre et Marie Curie Génétique et Biologie du École doctorale Complexité du Vivant developpement Institut Curie` CNRS U934 - INSERM UMR 3215 Transposon regulation upon dynamic loss of DNA methylation Thèse de Doctorat de Biologie présentée par Marius WALTER et dirigée par Déborah BOURC'HIS Présentée et soutenue le 10 Décembre 2015 devant un jury composé de: Dr. Antonin Morillon President du jury Pr. Wolf Reik Rapporteur Pr. Donal O'Carroll Rapporteur Dr. Vincent Colot Examinateur Dr. Michael Weber Examinateur Dr. Déborah Bourc'his Directrice de thèse 2 “There is large amount of evidence which suggests, but does not prove, that much DNA in higher organisms is little better than junk. […] We therefore need to explain how such DNA arose in the first place and why it is not speedily eliminated, since, by definition, it contributes little or nothing to the fitness of the organism.” Orgel and Crick, 1980 “In the future attention undoubtedly will be centered on the genome, and with greater appreciation of its significance as a highly sensitive organ of the cell, monitoring genomic activities and correcting common errors, sensing the unusual and unexpected events, and responding to them, often by restructuring the genome.” McClintock, 1983 “They didn’t know it was impossible so they did it.” Mark Twain 3 4 Acknowledgements I am grateful to the members of my jury who have agreed to evaluate my work: Pr. Wolf Reik and Pr. Donal O’Carroll, rapporteurs; Pr. Vincent Colot and Dr. Michael Weber, examinateur, and Dr. Antonin Morillon, president du jury. Being evaluated by such inspiring scientists is a rare privilege and I thank them in advance for their time and their help. This is a great honor. I started to write this PhD manuscript being convinced that it was a massive waste of time. Indeed, there was so little time left before I had to leave the lab and so many cool ideas I wanted to test… I had to reconsider this statement after a few weeks, being forced to realize that it was exactly the opposite: an incredible gift of time. I could finally read and learn. Writing became an incredibly inefficient process and I spent days lost in the literature, often chasing exotic transposons in obscure species. The frustration never went away, and in fact grew continuously as new ideas accumulated and time to test them inexorably disappeared. Nonetheless, in the end I really enjoyed it. I therefore want to thank very warmly the members of my jury who have to read this manuscript. I really hope they will enjoy it. To anybody else that would ever read this thesis, even a small part, or would just look at the figures and find them pretty, please send an email at [email protected]. I would add your name in the acknowledgment. Nothing could make me happier than being read, especially if you randomly found this thesis somewhere in the Internet. Please, really, send an email! I joined the lab of Deborah Bourc’his almost five years ago. My interest for biology was three months old and I had only a vague idea of what was DNA. Deborah nonetheless gave me a pipette, put me in the arms of two brave postdocs, and it was the start of an incredible human and scientific adventure. I have been incredibly lucky to work in this lab and with Deborah. I could not have been freer to do everything I wanted, nor receive better mentoring. I always had the help, the support and the trust of Deborah, which is invaluable. After five years spent in her lab, I feel that I think and act like a scientist. I am incredibly grateful for that. But what made my PhD such a wonderful experience is also the general atmosphere of the team and the department, a powerful mixing of scientific passion and true friendship. I especially want to thank Max and Joan, postdocs in the lab. Their curiosity, their apparently infinite knowledge and dedication for science constantly pushed me forward. They will never actually believe that I wrote that, but they represent the models of the young scientist I wanted to become. Beside, my debt to them (expressed in liters of beers they paid for me) is so staggering that it could never be repaid. Natasha also occupies a very special place. She introduced me to the fantastic world of transposons and with her strange Australian accent, she is probably the best English teacher I ever had. Having my first (and for the moment only) paper published with her means a lot to me. She is one of the closest friends I made here, and was present at very important time. I never believed she would actually leave, but the lab and the whole BDD are now missing their rightful Queen. That being said, we will all probably become half deaf very young because of her, but well J. I cannot write a paragraph for everybody, but I really enjoyed working with all the members of the team. Rachel that left too early, Raquel that is the nicest person I ever met, Julian that patiently taught me how to dissect tiny embryos, Tomek with its language impossible to master, Sophie that brought the world “crazy” to a new dimension. In a few 5 months I will transmit my crown of senior PhD to Juliane and I know she will make a good usage of it. I wish her all the failure she is impatiently looking for. Finally, I am incredibly grateful to Aurelie. I had the chance to work with her on a daily-basis on the bioinformatic analysis for more than a year and I consider myself incredibly lucky. I could never have done half of what I needed without her help and I could not be more thankful. I am conscious that working with me was not always easy and that I often asked too much, but I think that at the end it was worth it. I am fully aware of what I owe her and I think that we can be proud. I also want to acknowledge all the people in the department that contributed to my PhD, and especially all the team leaders. Their continual guidance during the course of this project, in unit seminars, thesis committees or elsewhere was very valuable and helpful. I especially want to thank Edith Heard, Raphael Margueron and their respective teams. I really learned a lot working in close contact with them. In particular, Michel and Elphège have been incredibly helpful, both in terms of technical help and scientific exchange. I cannot think about a better place to work than BDD, our department. And I should really write “live” and not “work” here, since I barely left the lab on this last year. At the end of my second year of PhD almost one year ago, I decided that I would finish it in three years instead of four. This manuscript shows it was possible, but at that time nobody believed I could do it. As consequence I seldom left the lab. The life of PhD students and postdocs sometimes involves insane amount of work. I survived because I could share that with close friends from all over the world. This department is full of amazing people, making almost unnecessary to maintain a social life out of it. Some might find that it is too much sometimes, but I had an amazing year. “Work hard, party hard” could definitely be the motto for PhDs and postdocs of our department. This is not the place to elaborate on that, but I want nonetheless to mention some of the people that contributed to the Friday night usual craziness. They made me happy during tough time, and I thank them for that. Neuza because she is the best, for real; Joke, my climbing partner that once did the biggest baby step ever; Diana, because she is worth a hundred bubbles and is a very good ; Eskeww, the black devil that we should never listen to; Anahi because she is Anahi; Tim, because we are the proof that European Union works, Natasha, undisputed Queen of BDD; Ellis and Eve for making sure that Max would stay in France forever; Raquel, because she is the voice of reason; Juliane after midnight, because this is another person; Joan, for being always there with me on the late night shifts; Simao, of course; Sophie, for pushing the limit another step further every time; Ines, one of my numerous Portuguese teacher; The WOS, best bar of Paris, therefore the world, why would anybody want to go anywhere else ?; MacDonald, for 1! hamburgers; My bike, that always knew the way home; Jennifer Doudna and Emmanuelle Charpentier, for changing the word, the French state, for giving money to have fun in the lab; Adobe Illustrator, my one true love; The Point Ephemere, the only reason not to go to the WOS, and finally the girls of BDD, my sun and stars.