基于生物信息计算的核小体定位动态机制研究

项目名称： 基于生物信息计算的核小体定位动态机制研究

项目编号： No.61272380

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 自动化技术、计算机技术

项目作者： 周水庚

作者单位： 复旦大学

项目金额： 81万元

中文摘要： 核小体是染色质的基本组元，由DNA缠绕在组蛋白八聚体上构成。核小体定位系指组蛋白八聚体在DNA 双螺旋上的精确位置，它与基因转录、DNA复制和修复等基本生命过程密切相关。发现核小体定位的机制是一项具有重要学术价值的挑战性课题。目前，人们主要基于组蛋白对DNA偏好性等静态因素研究核小体定位机制，而DNA序列偏好性并不能解释细胞在不同生理状态下核小体定位的差异。随着高通量实验技术的发展，不同生物、同一生物的不同细胞、同一细胞的不同生理状态等情况下的核小体分布数据越来越多，为探究核小体定位的动态影响因素创造了条件。本课题将集成不断涌现的核小体定位数据，基于生物信息计算，研究影响核小体定位的动态因素（如 DNA 甲基化、组蛋白修饰、染色质重塑因子和转录因子、染色质高级结构等），探索它们是如何协同调控核小体定位，从而揭示核小体定位的动态机制，建立更准确的核小体定位预测模型。

中文关键词： 生物信息学；表观遗传学；核小体定位；组蛋白修饰；预测模型

英文摘要： Nucleosome is the basic packaging unit of eukaryotic chromatin, which consists of about 146 base pairs DNA wrapped around a histone octamer. The location of histone octamer on the DNA sequence is called nucleosome positioning, which modulates the accessibility of regulatory proteins to DNA and thus influences eukaryotic gene regulation. Discovering the mechanisms underlying nucleosome positioning in-vivo is essential to understanding the binding and action of proteins that carry out essential genetic functions. The growing genome-wide data of in-vivo and in-vitro nucleosome positioning greatly advances the understanding of DNA sequence preferences that can influence nucleosome positioning. However, studies have shown that the influence of DNA sequence preferences is limited. An emerging picture is that the dynamic control of nucleosome positioning is governed by contributions from some dynamic factors, including DNA methylation, histone variants and posttranslational modifications, higher order chromatin structures, the actions of transcription factors, chromatin remodelers and other DNA-binding proteins. This project is proposed to investigate how these dynamic factors above function on nucleosome positioning, and analyze in which ways they might be integrated into a unified framework that accounts for both the

英文关键词： Bioinformatics；Epigenetics；Nucleosome positioning；Histone modification；Prediction model