摘要

Nucleosome deposition across genomic DNA is not random, but shows prominent features, which in turn regulates packaging of higher-ordered chromatin structure and gene transcription. ATP-dependent chromatin remodelers alter the positions of nucleosomes, and play major roles in control of chromatin structure and gene activity. Dysregulation of chromatin remodeling machinery is tightly implicated in a broad spectrum of human diseases, highlighting its critical biomedical relevance. Elucidating the molecular mechanisms underlying chromatin remodeling is therefore of fundamental significance and offers transformative future for the development of novel targeted therapeutics.

Over the past decade, our laboratory has uncovered fundamental mechanisms of chromatin remodeling, spanning the chemo-mechanical ATPase cycle that powers DNA translocation, the assembly of large multi-subunit remodeling complexes, and novel activities in subnucleosome remodeling. Importantly, these basic discoveries establish novel actionable strategies for drug development by targeting the vital parts of chromatin remodeling machineries. Here, I will discuss our ongoing research with promising translational potential for the treatment of cancer and neurodevelopmental disorders.

主讲人介绍

陈柱成，清华大学生命科学学院教授。先后于美国康奈尔大学获理学博士学位、在西南医学研究中心完成博士后研究，2011年加入清华大学。他系统解析了 SWI/SNF、ISWI 等染色质重塑蛋白及其复合体的三维结构，深入揭示了染色质重塑的机制。这些原创性成果为解析表观遗传信息的精准读取与编辑提供了结构基础，深化了人们对基因表达调控、DNA 损伤修复等核心生命过程的理解，也为相关疾病的机理研究与靶向药物开发奠定了重要理论支撑。相关研究成果多次发表于Nature、Science等国际顶级学术期刊。陈柱成教授于 2018 年获国家杰出青年科学基金资助，2025 年入选新基石研究员。