IQB Handbook

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29ACHIEVEMENTPUBLICATIONYamaguchi K, Hada M, Fukuda Y, Inoue E, Makino Y, Katou Y, Shirahige K, Okada Y. Re-evaluating the Localization of Sperm-Retained Histones Revealed the Modification-Dependent Accumulation in Specific Genome Regions. Cell Rep. 2018 Jun 26;23(13):3920-3932. DOI:10.1016/j.celrep.2018.05.094Makino Y, Jensen NH, Yokota N, Rossner MJ, Akiyama H, Shirahige K, Okada Y. Single cell RNA-sequencing identified Dec2 as a suppressive factor for spermatogonial differentiation by inhibiting Sohlh1 expression. Sci Rep. 2019 Apr 15;9(1):6063. DOI: 10.1038/s41598-019-42578-zOrganizer : International Symposium for Researchers in Chromatin Biology & EMBO lab management course. 2019 JuneOKADAYUKIPH.D. (2002) HOKKAIDO UNIVERISITYPOSTDOCTORAL FELLOW (2002) HOKKAIDO UNIVERISITYRESEARCH FELLOW (2003) UNIVERSITY OF NORTH CAROLINAAT CHAPEL HILL/HHMI PROJECT RESEARCH ASSOCIATE (2009) KYOTO UNIVERSITYPROJECT ASSOCIATE PROFESSOR (2012) INSTITUTE OF MOLECULAR AND CELLULAR BIOSCIENCES, THE UNIVERSITY OF TOKYOASSOCIATE PROFESSOR (2016) INSTITUTE OF MOLECULAR AND CELLULAR BIOSCIENCES, THE UNIVERSITY OF TOKYOPROFESSOR (2020) IQB / INSTITUTE FOR QUANTITATIVE BIOSCIENCES, THE UNIVERSITY OF TOKYO●MEMBER■ PROFESSOR :OKADA YUKI■ RESEARCH ASSOCIATE :MAKINO YOSHINORI■ RESEARCH ASSOCIATE : FUJIWARA YASUHIRO■ TECHNICAL SPECIALIST : INOUE ERINA■ TECHNICAL SPECIALIST :FUKUDA YUKO■ PROJECT ACADEMIC SUPPORT STAFF : YOSHIKAI KIYOHITOPUBLICATIONSYMPOSIUMe are investigating the relationship between epigenetic changes and cellular functions during male germ cell development (a.k.a. spermatogenesis). During spermatogenesis, various epigenetic events such as incorporation of histone variants into chromatin and histone-protamine exchange occurs. In addition, it’s recently suggested that these epigenetic marks are transgenerationally inherited to the next generation through sperm. Therefore, we are trying to elucidate the molecular mecha-nisms of spermatogenesis-specific chromatin regulation and transgenerational effects through the following approaches.1) Investigating the localization and transgenera-tional effects of sperm-retained histonesIn mature spermatozoa, 1~10 % (depending on animal species) are retained in chromatin, while their genomic localization has been controver-sial due to the technical issues of experiments. We successfully developed a method for sperm chromatin analyses, and demonstrated the genomic localization of sperm-retained histones by next-generation sequencing. We are currently expanding this system to other animal species to see what properties are conserved or different among animals. Further-more, we are also trying to elucidate the transgenerational effects of sperm-retained histones using mouse models.2) Investigating meiosis-specific chromatin structure and transcriptional regulationMeiotic chromosomes possess unique chromatin structure such as synaptonemal complex. Simultaneously, meiotic cells start to express large number of meiosis-specific genes. Howev-er, the correlation between these two events is largely unknown. We are investigating the molecular mechanism of meiosis-specific transcriptional regulation by using knockout mice with meiotic defects. 3) Investigating heterogeneity of spermatogonial stem cells Recent studies suggest that spermatogonial stem cells, the origin of spermatogenesis, consist of heterogenous population. We are trying to identify subpopulations of spermatogonial stem cells and their differences at molecular levels. W(1) Establishment of “VC mice”, in which spermatogenesis is visualized by fluorescence (2) Phosphorylated TH2A is a new chromatin condensation marker specific for germ cells (3) In vitro decondensa-tion of sperm chromatin and localization of sperm-retained histones (4) Heterogeneity and transcriptional wave of undifferentiated spermatogonia analyzed by single cell RNA-seq