Set7 : a new protein involved in the epigenetic mechanisms underlying male infertility

Schizosaccharomyces pombe Set7 protein, belonging to the histone-methyltransferase (HMT) family, was identified and characterized. HMTs are involved in the histone methylation mechanism, so they play a key role in transcriptional regulation. The study of the interactions between HMT and their different substrates is therefore extremely important for the understanding of the mechanisms that regulate gametogenesis and / or spermatogenesis. The research came from the collaboration between the Institute of Crystallography (CNR-IC) of Bari [group of Dr. Caliandro] and the Kyungpook National University of Daegu (South Korea) [group of Dr. di Luccio], due to a bilateral project funded by the CNR and the Korean National Research Foundation, and was published by the prestigious international journal Structure (CellPress).Set7 shows a unique amino acid sequence between the known HMTs and the structurally closest homologous has a low sequence identity (≈ 23%). The determination of its atomic structure (shown in  the figure) by means of X-ray diffraction was possible only through the use of latest generation algorithms, implemented in SIR2014, an automatic software developed and distributed by CNR-IC researchers. Set7 in crystalline form is a homo-dimer, a rather rare configuration for this type of protein. The research led to clarify the methylation mechanism and the role of Set7 protein in the epigenetic regulation process of S. pombe gametogenesis. This study proved that methylation levels increase dramatically during gametogenesis and that Set7 deletion mutant cells show defects and produce an abnormal number of spores with aberrant morphology. These results support the link between Set7 protein, H3K37 epigenetic mark and the correct gametogenesis in S. pombe. Since S. pombe gametogenesis shows similarities with mammalian spermatogenesis, these findings pave the way for a better understanding of the human male infertility.

Shen Y, Mevius DEHF, Caliandro R, Carrozzini B, Roh Y, Kim J, Kim S, Ha SC, Morishita M, di Luccio E. “Set7 Is a H3K37 Methyltransferase in Schizosaccharomyces pombe and Is Required for Proper Gametogenesis” Structure 27 2019. doi: 10.1016/j.str.2019.01.011.