Meiotic sex chromosome inactivation and the XY body: a phase separation hypothesis

Cell Mol Life Sci. 2021 Dec 31;79(1):18. doi: 10.1007/s00018-021-04075-3.


In mammalian male meiosis, the heterologous X and Y chromosomes remain unsynapsed and, as a result, are subject to meiotic sex chromosome inactivation (MSCI). MSCI is required for the successful completion of spermatogenesis. Following the initiation of MSCI, the X and Y chromosomes undergo various epigenetic modifications and are transformed into a nuclear body termed the XY body. Here, we review the mechanisms underlying the initiation of two essential, sequential processes in meiotic prophase I: MSCI and XY-body formation. The initiation of MSCI is directed by the action of DNA damage response (DDR) pathways; downstream of the DDR, unique epigenetic states are established, leading to the formation of the XY body. Accumulating evidence suggests that MSCI and subsequent XY-body formation may be driven by phase separation, a physical process that governs the formation of membraneless organelles and other biomolecular condensates. Thus, here we gather literature-based evidence to explore a phase separation hypothesis for the initiation of MSCI and the formation of the XY body.

Keywords: Epigenetics; Germ cells; Germline; Liquid–liquid phase separation; Sex body; Sex chromosomes.

Publication types

  • Review

MeSH terms

  • Animals
  • DNA Damage / genetics
  • DNA Repair / genetics
  • Dosage Compensation, Genetic*
  • Humans
  • Meiosis* / genetics
  • Models, Biological*
  • Sex Chromosomes / metabolism*