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

• Published in: Cellular and molecular life sciences : CMLS Vol. 79; no. 1; p. 18
• Main Authors: Alavattam, Kris G., Maezawa, So, Andreassen, Paul R., Namekawa, Satoshi H.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-01-2022; Springer Nature B.V
• Subjects: Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Chromosomes; Deactivation; DNA damage; DNA Damage - genetics; DNA Repair - genetics; Dosage Compensation, Genetic; Epigenetics; Humans; Hypotheses; Inactivation; Life Sciences; Meiosis; Meiosis - genetics; Models, Biological; Organelles; Phase separation; Prophase; Review; Sex; Sex chromosomes; Sex Chromosomes - metabolism; Spermatogenesis; Y chromosomes; Liquid–liquid phase separation; Epigenetics; Sex chromosomes; Sex body; Germ cells; Germline
• ISSN: 1420-682X; 1420-9071
• 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.