Polycomb group (PcG) proteins prevent the assembly of higher order repetitive structures during meiosis
Authors: Bruno Marques 1; Tália Feijão 1,3; Rui Silva 1,2; Daniel Sobral 4; Ricardo Matos 1; Célia Carvalho 5; Antonio Pereira 3; Eurico Morais de Sá 3; Hélder Maiato 3; Rui Gonçalo Martinho 1,5,6
Affiliations: 1) Algarve Biomedical Center Research Institute (ABC-RI), Universidade do Algarve, 8005-139 Faro, Portugal; 2) Faculty of Medicine and Biomedical Sciences (FMCB), Universidade do Algarve, 8005-139 Faro, Portugal; 3) i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal; 4) Associate Laboratory i4HB - Institute for Health and Bioeconomy, and UCIBIO - Applied Molecular Biosciences Unit, Department of Life Sciences, School of Science and Technology, NOVA University Lisbon, 2819-516 Caparica, Portugal; 5) Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal; 6) Department of Medical Sciences and Institute for Biomedicine (iBiMED), Universidade de Aveiro, 3810-193 Aveiro, Portugal
Keywords: b. oogenesis; j. epigenetics
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 higher order repetitive structures, which are not assembled between the paired homologs and whose formation is potentially deleterious for meiosis and gametogenesis. This creates an interesting conundrum, where SC genes need to be robustly expressed during mitotic to meiotic transition, but their expression must be carefully regulated to prevent the formation of abnormal SC structures. In this manuscript, we show that the Polycomb group protein Sfmbt, the Drosophila ortholog of human MBTD1 and L3MBTL2, is required to avoid excessive expression of SC genes during prophase I. Although SC assembly is normal after Sfmbt depletion, SC disassembly is abnormal with the formation of a complex network of alternative SC structures (polycomplexes) within the oocyte. Overexpression of the SC gene 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. Polycomb group proteins are therefore crucial for coherent gene expression during prophase I.