A missing link in male meiotic sex chromosome inactivation:the effectors of DDR factors
In mammalian male meiosis,the X and Y chromosomes only synapse in the pseudoautosomal region,and the extensive unsynapsed regions trigger meiotic silencing of sex chromosomes(MSCI).MSCI is essential for spermatogenesis and,upon its initiation,leads to a remodeling of the X and Y chromosome structure,forming a distinct region separated from the autosomes,known as the XY body.In this study,we review the mechanisms underlying MSCI and XY body formation.The initiation of MSCI is mediated by the DNA damage response(DDR)pathway.Downstream of DDR,multiple pathways are involved;however,there is a gap in the evidence chain regarding the mechanisms from late pachytene to early/mid-diplotene.Additionally,increasing evidence suggests that MSCI and subsequent XY body formation may be driven by phase separation,a physical process governing the formation of membrane-less organelles and other biomolecular condensates.Here,we review recent studies on the mechanisms of MSCI and liquid-liquid phase separation(LLPS),highlighting the potential link between LLPS and XY body,and discuss the challenges for further investigation.
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