AbstractExternal stimuli and stress in living organisms are ultimately transmitted to cells through various signaling pathways. Cells that perceive these stimuli or stresses activate the expression of genes necessary to respond. Our previous studies have shown that the Mediator complex containing MED26 coordinately activates the transcription of distinct gene sets through its association with two different transcription elongation complexes: the Super Elongation Complex (SEC) and the Little Elongation Complex (LEC). In this study, we demonstrated that the Mediator complex including MED26 forms specialized nuclear compartments ("condensates") via liquid–liquid phase separation, which facilitates the coordinated transcription of tumor-related and stress-responsive genes (manuscript in preparation). Moreover, we found that in cervical cancer cells caused by human papillomavirus infection, MED26 and SEC form a condensate known as a super-enhancer upstream of the c-Myc gene, promoting cancer cell proliferation. To further elucidate such condensate-mediated transcriptional regulatory mechanisms, we developed a novel technique—in situ biotinylation—for comprehensive identification of the components of nuclear condensates and structures. MED26-mediated transcriptional regulation has emerged as a critical mechanism during periods requiring rapid RNA synthesis, such as stress responses and stem cell differentiation, and we are currently preparing a manuscript for publication.はじめに近年,ゲノムワイドな ChIP(クロマチン免疫沈降)シークエンスなどの解析により,遺伝子によっては,転写開始後に RNA ポリメラーゼ II(以下 Pol II)がプロモーター近傍(転写開始点から20 ~ 50 塩基下流)や転写終結領域で一時停止していることが明らかになり,遺伝子発現の制御に横浜市立大学大学院医学研究科分子生物学分野・教授Department of Molecular Biology, Graduate School of Medicine,Yokohama City University高橋 秀尚Hidehisa Takahashi― 46 ―メディエーター複合体の液滴による新たな遺伝子発現制御機構の解明Elucidation…of…a…novel…gene…expression…mechanismthrough…liquid…droplets…formation…by…Mediator…Complex
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