中国科学院生物物理研究所,表观遗传调控与干预重点实验室,研究组长 中国科学院大学岗位教授
1992 - 1999 湖南师范大学,学士,硕士
1999 - 2003 中国科学院上海生物化学与细胞生物学研究所,博士
2003 - 2011 美国国立卫生研究院癌症研究所(NIH, NCI), 博士后
2011 - 中国科学院生物物理研究所,研究员
染色质结构的动态变化是表观遗传调控的重要基础,与DNA复制、基因转录、DNA损伤修复、基因组稳定性维持等重要生物学事件密切相关。染色质动态源于DNA或组蛋白的序列及化学性质的改变,以及核小体组成和染色质结构的差异,同时也受到组蛋白变体、组蛋白伴侣、组蛋白修饰酶、染色质重塑复合物、非编码RNA等多种表观因子的调节。
本课题组关注的科学问题是染色质动态的调控及功能,我们将运用包括冷冻电镜在内的多种结构生物学手段,结合生物化学、生物物理学、酵母遗传学、单分子力谱、计算生物学等方法,开展两个方向的研究:
1. 核小体编辑
研究染色质重构复合物如何催化组蛋白变体对常规组蛋白进行替换,以及如何实现核小体编辑的人工操控。核小体编辑通过将组蛋白H2A变体精准定位到基因组特定区域进行基因表达调控,其功能异常与癌症等多种疾病密切相关。阐明核小体编辑的作用机制有助于新型表观遗传编辑技术的研发(图一)。
2. DNA损伤修复调控
研究细胞如何选择特定的修复途径对DNA损伤进行修复。DNA损伤"合成致死"效应在癌症治疗中的作用,催生了PARP抑制剂等一线抗癌药物,阐明DNA损伤修复的调控机制有助于发现新的药物靶点,促进抗癌药物的研发(图二)。
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3. Huang Y,Zhou Z. (2018) Recent progress in histone chaperones associated with H2A-H2B type histones.Prog Biochem Biophys. 45(9): 971-980. (review)OPEN
4. Zhou J, Feng X,Zhou Z. (2015) Chromatin assembly of histone variants.Prog Biochem Biophys.42(11):1003~1008. (review)OPEN
(资料来源:周政研究员,2024-09-14)