Regulation of chromatin remodelling and gene expression during meiosis and Oocyte maturation

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Transcriptional regulation of Synaptonemal complex assembly and disassembly during meiosis

Publication . Marques, Bruno Filipe Pinheiro; Martinho, Rui Gonçalo; Bragança, José

Human female meiosis can take several decades to be concluded, as the oocytes enter meiosis before birth and stay arrested in prophase I in a dormant state until puberty. We aim to better understand the mechanisms responsible for the correct awakening of the oocyte, and the way they ensure successful meiotic progression and oocyte maturation. We and others showed that the prophase I-arrested Drosophila oocyte is transcriptionally quiescent for approximately 36 hours, and similarly to human oocytes, its reactivation is associated with a poorly understood global remodelling of its chromatin architecture. A screen for endogenously GFP-tagged transcription factors allowed the identification of Polycomb as being highly enriched in the oocyte chromatin and we will present our ongoing work related with the function of this protein complex and our attempts to visualize oocyte reactivation using live-cell imaging techniques. Additionally, the synaptonemal complex (SC) is a proteinaceous scaffold that is assembled between the paired homologous chromosomes during the onset of meiosis. The SC stabilizes chromosome pairing and is important for crossovers formation, recombination and accurate segregation of meiotic chromosomes. Timely expression of SC genes is essential for SC assembly and successful meiosis. However, SC components have an intrinsic tendency to self-organize into alternative repetitive structures (polycomplexes), being potentially deleterious for meiosis and gametogenesis. In this work, we show that Sfmbt, is required to avoid excessive expression of SC genes during prophase I and consequently formation of polycomplexes during SC disassembly. Overexpression of Corona and depletion of other Polycomb group proteins are similarly associated to polycomplexes formation during SC disassembly. These polycomplexes are highly dynamic and have a well-defined periodic structure. Further confirming the importance of Sfmbt for female gametogenesis, germ line depletion of this protein is associated to significant metaphase I defects and a reduction of female fertility.

2022-03-24Doctoral thesis

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