含组蛋白变体H3.3核小体组装和去组装的分子机制及其在表观遗传记忆调控中的功能研究

项目名称： 含组蛋白变体H3.3核小体组装和去组装的分子机制及其在表观遗传记忆调控中的功能研究

项目编号： No.91319304

项目类型： 重大研究计划

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 方玉达

作者单位： 中国科学院上海生命科学研究院

项目金额： 300万元

中文摘要： 为维持生物体个体正常发育和对环境的有效应答，细胞内一些基因的转录或沉默能在细胞分裂前后被“记住”，这可以是通过有丝分裂的短期记忆，也可是通过减数分裂的跨代长期记忆。这种表观遗传记忆是细胞编程和重编程的核心问题之一。生物体内非常保守的组蛋白H3变体H3.3在表观遗传记忆中起到重要的作用。最近我们发现当基因激活时，拟南芥H3.3核心区中的87和90位两个氨基酸介导H3.3加载到具转录活性的染色质上，而当基因沉默时，H3.3氨基端的31和41位氨基酸介导H3.3从核小体上解离。本项目拟以模式植物拟南芥为材料，在前期重要结果基础上，通过鉴定出组蛋白变体H3.3组装入核小体和从核小体上卸载过程中涉及的关键分子伴侣，从而明确含组蛋白变体H3.3的核小体组装和去组装调控的分子机制，进而回答H3.3介导的表观遗传记忆调控的分子基础。

中文关键词： 拟南芥；H3.3；分子伴侣；组蛋白修饰；组蛋白变体

英文摘要： To respond effectively to developmental and enviromental changes, the cells in organisms can “remember” the transcriptional or silencing statuses of genes. The memory can be short memory across mitosis or transgenerational long memory passing through meiosis. The epigenetic memory is one of the critical questions in programming and reprogramming of the cell. The conservative histone H3 variant H3.3 plays important roles in epigenetic memory. Recently, we found that the amino acid residues 87 and 90 in the core domain of Arabidopsis H3.3 guide its deposition to chromatin when the genes are activated, while the amino acid residues 31 and 41 in the N-terminal tail of H3.3 guide its depletion from chromatin when the genes are silenced. Based on our previous important findings, in this project, we plan to identify the key chaperones for the assembly of H3.3 into the nucleosomes and disassembly of H3.3 from the nucleosomes, then define the molecular mechanisms for the regulation of these processes, and address the molecular bases for the regulation of H3.3-mediated epigenetic memory.

英文关键词： Arabidopsis；H3.3；chaporone；histone modification；histone variant