旭硝子財団助成研究成果報告2023

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旭硝子財団　助成研究成果報告（2023）through interactions with other cells in addition to cell intrinsic regulation. However, the molecular mecha-nisms that regulate production of cellular diversity has been stalled because the cell non-utonomous regulato-ry mechanisms remain unclear. We found that ectopic expression of Ey/Pax6 in neurons dramatically in-creased the number of glial cells produced from neural stem cells, suggesting that neurons alter neural stem cell properties via some secretory factor(s). In this study, we narrowed down the candidates of the secretory factors via transcriptome and expression analysis.グラム陰性の低温適応細菌Shewanella vesiculosa HM13は，細胞外膜小胞（Extracellular membrane vesicles, EMVs）の主要な積荷として選択的に機能未知タンパク質P49を細胞外に輸送する．EMVsを介した選択的な積荷タンパク質輸送機構は，新規の異種タンパク質生産系開発への展開が期待される．本研究では，P49選択的なEMVsへの積荷輸送機構の解明に取り組んだ．その結果，P49遺伝子の下流に存在するWzx flippaseが本菌の細胞およびEMVsの表層多糖の合成を担うことを見いだした．さらに，Wzxを欠損したことでEMVsにP49が積み込まれなかったことから，Wzx依存的な経路で合成される表層多糖がP49のEMVsへの積み込みにおける足場として機能することがわかった．Shewanella vesiculosa HM13, a Gram-negative bacterium isolated from fish intestines, secretes a large number of extracellular membrane vesicles (EMVs) carrying a functionally unknown protein P49 as a single major cargo. This selective cargo transportation via vesiculation has a potential application to the development of a secretory production system of heterologous proteins. In this study, we focused on the molecular mechanism of the cargo-selective loading to EMVs of this bacterium. As a result, a homolog of Wzx flippase encoded by a downstream gene of the P49 gene was found to be essential for the biosynthesis of capsular polysaccharides (CPS) of this bacterium. Moreover, the defect of the CPS resulted in the disassociation of P49 and EMVs, in-dicating that CPS function as a scaffold of P49 on the EMV surface.ヒストンは様々な翻訳後修飾を受けることで，クロマチン構造及び遺伝子発現の動的な制御に関与している．ヒストン修飾の異常は，がん・免疫疾患・代謝疾患など様々な疾患に関わることが報告されており，ヒストン修飾を人工的に導入することができれば，疾患の原因解明および治療につながることが期待されている．本研究では，エピジェネティクス関連疾患治療を見据えた化学触媒の開発を目的とする．具体的な目標としては，生細胞内で働く化学触媒を開発し，人工的H2BK120アシル化とそれに伴うH2BK120ユビキチン化阻害が可能な系を構築する．Histones are involved in the dynamic regulation of chromatin structure and gene expression by undergoing various post-translational modifications. Abnormal histone modifications have been reported to be involved in various diseases such as cancer, immunological diseases, and metabolic diseases, and the artificial intro-48川本　純47Jun KAWAMOTO川島　茂裕48Shigehiro KAWASHIMA細菌の外膜小胞を基盤とする低温バイオテクノロジーの開発（2022採択）Development of low-temperature biotechnology based on bacterial outer membrane vesicles(Project 2022)個体で機能する新規ヒストンアセチル化触媒の開発（2022採択）Development of a novel histone acetylation catalyst for in vivo applications(Project 2022)