202401Shimada

研究発表を行った学会；第46回日本分子生物学会年会
2023年12月6日〜8日（神戸市）
タイトル； 転写因子複合体STRA8-MEIOSINによる減数分裂遺伝子の転写活性化の分子機構.
発表者；島田　龍輝氏
（熊本大学　発生医学研究所　染色体制御分野）
要旨；
STRA8 and MEIOSIN activate temporal expression of meiotic genes to initiate meiosis. Prediction from their amino acid sequence suggests that mouse MEIOSIN possesses evolutionarily conserved HLH and HMG domains. Similarly, mouse STRA8 is predicted to possess HLH-like and HMG-like domains. Further, STRA8 possesses a LXCXE motif for RB binding, and a glutamic acid repeat (E-repeat), which represents a feature shared by transcriptional activators. To address the individual roles of STRA8 and MEIOSIN in transcriptional activation, putative functional domains were dissected by generating mutant mice that lacked individual ones. Co-immunoprecipitation analyses showed that STRA8 forms two distinct sub-complexes, STRA8-RB complex that is formed via a LXCXE motif of STRA8, and STRA8-MEIOSIN complex that is formed via their HLH domains. We demonstrated that the LXCXE motif in STRA8 is required for activation of E2F-target genes to progress into pre-meiotic S phase in female germ cells. Remarkably, even in the absence of STRA8-MEIOSIN interaction, germ cells were able to enter meiosis, but failed to progress through meiotic prophase both in Stra8∆HLH and Meiosin∆HLH. Similarly, Stra8∆E germ cells were able to enter meiosis, but showed a defect in progression of meiotic prophase. These phenotypes were in stark contrast to that observed in Meiosin-KO testis, in which the germ cells completely failed to enter meiosis and exhibited a mitotic-like character. Our observations suggest that MEIOSIN may possess an intrinsic ability to activate meiotic genes independently of STRA8. We discuss the molecular basis of meiotic initiation in terms of the evolutionary conservation and diversity.