The public defence will be held as a video conference over Zoom.
The defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.
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Due to copyright reasons, an electronic copy of the thesis must be ordered from the faculty. In order for the faculty to have time to process the order, it must be received by the faculty no later than 2 days prior to the public defence. Orders received later than 2 days before the defence will not be processed. Inquiries regarding the thesis after the public defence must be addressed to the candidate.
Digital Trial Lecture – time and place
Adjudication committee
- First opponent: Professor Leonie Ringrose, Humboldt Universität zu Berlin, Germany
- Second opponent: Associate Professor Paul Cloos, University of Copenhagen, Denmark
- Third member and chair of the evaluation committee: Professor Philippe Collas, University of Oslo
Chair of the Defence
Professor Erik Dissen, Faculty of Medicine, University of Oslo
Principal Supervisor
John Arne Dahl, Group Leader, Oslo University Hospital
Summary
The continuum of life requires survival and procreation. In mammals such as humans, this is achieved through a haploid-diploid life cycle. The transitions through the haploid-diploid life cycle require extensive epigenetic reprogramming of gametes and early embryos. In this thesis, we developed efficient µChIP-seq and picoChIP-seq methods suitable to study genome-wide histone modification profiles of small pools of cells and single cells. Using these methods, first, we revealed that, unlike in any other cell type, approximately 22% of the mouse oocyte genome is covered with broad H3K4me3 domains (bdH3K4me3) that are anti-correlated with DNA methylation. These domains are inherited to the early embryo and have a role in modulating the MZT. Second, we demonstrated that KDM4A (an H3K9me3 demethylase) regulates the MZT by protecting bdH3K4me3 from H3K9me3 invasion in oocytes, and the silencing effect of H3K9me3 can be rescued by the injection of catalytically active Kdm4a transcripts in the MII oocyte. Third, by using picoChIP-seq, we uncovered epigenetic heterogeneity of oocytes and identified that the establishment of thousands of late broad H3K4me3 domains is closely linked to the transition from the actively transcribing NSN oocyte stage to the quiescent SN oocyte stage. Finally, our comparative analysis of oocytes of multiple species showed that broad H3K4me3 domains cover large fractions of the oocyte genome in bovine, porcine and mouse, but less in human oocytes. However, the timing of bdH3K4me3 removal is conserved between mouse and human in that it takes place at the time of major zygotic genome activation (ZGA) in both species. Single-embryo ChIP-seq of human day-3 embryos identified a lack of bdH3K4me3 removal in some abnormal embryos. In summary, the work in this thesis demonstrates an important role for post-translational histone modifications in the oocyte for the acquisition of meiotic competence and early embryo development.
Additional information
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