O'Carroll lab paper featured in Nature Communications. Authors Image This study identifies TEX15 as an interaction of the PIWI protein MIWI2 and demonstrates that TEX15 is essential for piRNA-directed DNA methylation as well as transposon silencing in the male germline. Schöpp, T., Zoch, A., Berrens, R.V., Auchynnikava, T., Kabayama, Y., Vasiliauskaitė, L., Rappsilber, J., Allshire, R.C., and O’Carroll, D. Summary of Paper by Lori Koch In mammals, during sperm cell development the structure of the DNA is drastically altered to establish which genes are active or repressed. This is accomplished by a global erasure of methylation marks from the DNA and followed by a de novo methylation process. The loss of methylation can cause potentially harmful genes to become expressed, such as transposable elements which can insert into new locations in the DNA. In their recent study in Nature Communications, Teresa Schopp and their colleagues in the O’Carroll group identified the factor TEX15 to be an essential regulator of transposable element silencing via piRNA-mediated de novo DNA methylation during sperm development. They performed immunoprecipitation followed by mass spectrometry (IP-MS) of the MIWI2 protein from mouse foetal sperm precursors to identify interacting proteins and they recovered TEX15, but only under conditions where chromatin is solubilized during the procedure. Mutant mice lacking TEX15 are sterile, similar to other piRNA-pathway and de novo methylation mutants, and mutations in human TEX15 are associated with male infertility. RNA sequencing revealed that many transposable elements were de-regulated in male mouse sperm precursor cells lacking TEX15, and in fact the same set of transposable elements are de-regulated in MIWI2 mutants. Overall, the abundance and composition of piRNAs were unchanged in the absence of TEX15, suggesting that TEX15 works with MIWI2 after piRNA recruits them to DNA to promote methylation. Finally, methylation sequencing results demonstrated a lack of methylation in the same subset of transposable elements de-regulated in the absence of MIWI2. Overall, their data presents a model in which TEX15 associates with MIWI2 to promote essential de novo DNA methylation in sperm cell precursors. Related links Journal Link O’Carroll Lab Website DOI This article was published on 2024-06-17
