O'Carroll lab paper featured in Nature. Authors Image This study identifies SPOCD1 that links the de novo methylation machinery to the piRNA pathway and is essential for transposon methylation in the developing mammalian germline. Zoch, A., Auchynnikava, T., Berrens, R.V., Kabayama, Y., Schöpp, T., Heep, M., Vasiliauskaitė, L., Pérez-Rico, Y.A., Cook, A.G., Shkumatava, A., Rappsilber, J., Allshire, R.C., and O’Carroll, D. Summary of Paper by Lori Koch Germline cells have great potential - they create egg and sperm cells, which can produce a whole new organism. In mammals, germline cells are produced from somatic cells early during development. This "re-programming" requires dramatic changes in the chemical structure of the DNA, such as erasing and placing new methylation marks. During this process many genes that were previously kept inactive by the methylation marks become expressed, including transposable elements which, by "jumping" into new positions in the DNA, can cause a lot of damage. In their recent study published in Nature, a team of scientists led by Ansgar Zoch, a postdoc in Donal O'Carroll's group (WCB), performed experiments with male mice and identified a key protein required to curb transposable elements during sperm development. They started by analysing MIWI2, a protein that associates with piRNAs to restrict transposable elements, by immunoprecipitation and mass spectrometry (IP-MS). In their results, they identified the protein Spocd1 as a good candidate for further study. They generated mutant mice and found that Spocd1 deficiency caused dramatic male-specific infertility, with a complete absence of mature sperm. RNA-sequencing suggested that Spocd1 is not a general regulator of RNA or piRNA, but specifically functions in the MIWI2-piRNA pathway to repress certain transposable elements in the male germline. When they analysed Spocd1 by IP-MS, they found that it associates with the same DNA methylation enzymes required for de novo genome methylation. Overall, their work leads to a model in which Spocd1 binds MIWI2 to recruit DNA methylation enzymes that work to prevent expression of transposable elements during sperm development. Related links Journal Link DOI O’Carroll Lab Website This article was published on 2024-06-17
