Heat shock factor 5 establishes the male germ-line meiotic sex chromosome inactivation through regulation of Smarca4

Meiotic sex chromosome inactivation is an essential event in male germ cell development, which is directed by DNA damage response signaling independent of Xist RNA to silence the transcription activity of the sex chromosomes. However, the specific mechanism of establishment and maintenance of meiotic chromosome silencing is still unclear. Here we identify the HSF5 as a testicular specific protein and the expression of which was at the onset of meiosis pachytene stage to round sperm. When the function of the HSF5 was lost, meiosis sex chromosome remodeling and silencing fail, followed by activation of CHK2 checkpoint leads to germ cell apoptosis. Furthermore, we found that SMARCA4 in the linking the HSF5 to MSCI and uncover additional factors with meiotic sex chromosome remodeling. Together, our results demonstrate a requirement for HSF5 activity in spermatogenesis and suggest a role for the mammalian HSF5-SMARCA4 in programmed meiotic sex chromosome remodeling and silencing events that take place during meiosis.