SSTY proteins co-localize with the post-meiotic sex chromatin and interact with regulators of its expression

In mammals, X- and Y-encoded genes are transcriptionally shut down during male meiosis, but expression of many of them is (re)activated in spermatids after meiosis. Post-meiotic XY gene expression is regulated by active epigenetic marks, which are de novo incorporated in the sex chromatin of spermatids, and by repressive epigenetic marks inherited during meiosis; alterations in this process lead to male infertility. In the mouse, post-meiotic XY gene expression is known to depend on genetic information carried by the male-specific region of the Y chromosome long arm (MSYq). The MSYq gene Sly has been shown to be a key regulator of post-meiotic sex chromosome gene expression and is necessary for the maintenance/recruitment of repressive epigenetic marks on the sex chromatin, but studies suggest that another MSYq gene may also be required. The best candidate to date is Ssty, an MSYq multi-copy gene of unknown function. Here, we show that SSTY proteins are specifically expressed in round and elongating spermatids, and co-localize with post-meiotic sex chromatin. Moreover, SSTY proteins interact with SLY protein and its X-linked homolog SLX/SLXL1, and may be required for localization of SLX/SLY proteins in the spermatid nucleus and sex chromatin. Our data suggest that SSTY is a second MSYq factor involved in the control of XY gene expression during sperm differentiation. As Slx/Slxl1 and Sly genes have been shown to be involved in the XY intra-genomic conflict, which affects the offspring sex ratio, Ssty may constitute another player in this conflict.