Polycomb group (PcG) proteins prevent the assembly of abnormal synaptonemal complex structures during meiosis

Copyright © 2022 the Author(s). Published by PNAS. This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).The synaptonemal complex (SC) is a proteinaceous scaffold that is assembled between paired homologous chromosomes during the onset of meiosis. Timely expression of SC coding genes is essential for SC assembly and successful meiosis. However, SC components have an intrinsic tendency to self-organize into abnormal 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 meiosis, but their expression must be carefully regulated to prevent the formation of anomalous 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 multiple synaptonemal complexes (polycomplexes) within the oocyte. Overexpression of the SC gene corona and depletion of other Polycomb group proteins are similarly associated with polycomplex formation during SC disassembly. These polycomplexes are highly dynamic and have a well-defined periodic structure. Further confirming the importance of Sfmbt, germ line depletion of this protein is associated with significant metaphase I defects and a reduction in female fertility. Since transcription of SC genes mostly occurs during early prophase I, our results suggest a role of Sfmbt and other Polycomb group proteins in downregulating the expression of these and other early prophase I genes during later stages of meiosis.R.G.M. is supported by Portuguese national funding through Fundação para a Ciência e a Tecnologia (FCT grant refs. PTDC/BIA-BID/28441/2017 and PTDC/BIA-BID/1606/2020). B.M. and R.D.S. are both supported by Portuguese national funding through Fundação para a Ciência e a Tecnologia, respectively, PD/BD/128342/2017 (within the scope of the ProRegeM PhD program; PD/00117/2012, CRM:0027030) and DL 57/2016/CP1361/CT0019. The Light Microscopy Unit of ABC-RI was partially supported by Portuguese national funding (FCT: PPBI-POCI-01-0145-FEDER-022122). This work was developed with the support of the research infrastructure Congento (project LISBOA-01-0145-FEDER-022170). The Transgenic RNAi Project (TRiP) collection at Harvard Medical School was supported by NIH/NIGMS R01-GM084947.info:eu-repo/semantics/publishedVersio