基于细胞周期变化特征的染色质三维结构模型

项目名称： 基于细胞周期变化特征的染色质三维结构模型

项目编号： No.31501081

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 杨清竹

作者单位： 中国科学院北京基因组研究所

项目金额： 20万元

中文摘要： 染色质在细胞核中存在高度精密的折叠，这种折叠结构与基因组功能高度相关。近年来染色质三维结构研究在新技术的推动下发展迅速，然而现有的模型对很多新的实验现象缺乏足够的解释力。本课题拟从染色质的细胞周期变化特征出发，运用多聚体物理学和统计模拟，构建染色质结构模型。染色质的周期变化特征，从细胞分裂过程中的染色质聚合和扩散现象抽象归纳出。然后，运用Hi-C，FISH实验数据验证并改进模型，并预测现有观测数据中染色质预存结构的比例，以及细胞周期中保守的染色质相互作用的比例。最后，利用该模型阐释包括染色质预存结构，部分染色质相互作用在细胞周期中的保守性，染色质环附近的CTCF对的方向会聚性等新近实验观测现象的机理。本课题的研究，将为染色质空间结构相关的生物学现象提供新的结构学阐释，并促进对基因组调控机理的理解。

中文关键词： 动物；生物大分子；染色体；结构；模型

英文摘要： Chromatin is extensively folded in the nucleus. Genome function is tightly correlated with chromatin folding. Recently, the development of the research on chromatin structure has grown rapidly due to the promotion of new technology. However, the existing models cannot provide persuasive explanations for quite a few experimental phenomena. This project will construct a new model of three-dimension chromatin structure using the principles of polymer physics and methods of statistical simulation based on the chromatin dynamics of cell cycle. Chromatin dynamics will be generalized from the process of aggregation and diffusion of chromatin during cell division. Then we will use the Hi-C data and FISH data to test and improve the model. The model will be used to predict the proportion of the pre-existing chromatin looping in the observed data and the conserved chromatin interactions during cell cycle. At last, we try to explore the mechanism of the related biological phenomena from the model, e.g., the pre-existing chromatin looping, the conservation of partial chromatin interactions during cell cycle and the vast majority of chromatin loops associated with pairs of CTCF motifs which are in a convergent orientation. This project will provide new structural explanation for the biological phenomena correlated with the chromatin structure and help to understand the mechanism of genome regulation more clearly.

英文关键词： animal;biomacromolecule;chromosome;structure;model