基于DNA变形能的核小体定位预测方法研究进展

Advances in DNA deformation energy-based methods for predicting nucleosome positioning

真核细胞中,作为染色质基本结构单元的核小体参与调控基因的转录、DNA复制、重组以及RNA剪接等诸多生物学过程。阐明核小体定位机制并准确预测核小体在染色体上的位置对解读染色质结构与功能有重要生物学意义。在过去30多年时间里,研究人员发展了多种预测核小体位置的方法。最理想的方法应考虑DNA序列、组蛋白修饰和染色质重塑等影响核小体定位的诸多因素,然而现实中,捕捉主要因素的模型也往往具有很高的鲁棒性和实用价值。DNA序列偏好性是在全基因组尺度上影响核小体定位的最重要因素之一,因此基于DNA序列的核小体定位预测方法也最常见。这种方法可大致分为两类,即基于DNA序列信息的生物信息学模型和基于DNA变形能的生物物理学模型。本文重点介绍生物物理学模型近些年取得的主要进展。

Nucleosome is the fundamental structural unit of chromatin in eukaryotes,which regulates various biological processes such as gene transcription,DNA replication,meiotic recombination,and RNA splicing.Decoding the mechanism of nucleosome positioning and the accurate prediction of the positions of nucleosomes along the genome are of great significance for the understanding of the chromatin structure and functions.In the past three decades,many methods for predicting nucleosome positioning have been proposed.Models designed to capture the important aspects of nucleosome positioning always exhibit high robustness with a wide range of applications,although,in an ideal model,various factors like DNA sequence preference,histone modifications,and chromatin remodeling should be considered.DNA sequence preference is one of the most important factors that influences the genome-scale nucleosome organization.Therefore,many sequence-dependent models for predicting nucleosome positioning have been developed,which can be roughly classified into two major categories:sequence information-based bioinformatic models and deformation energy-based biophysical models.Recent progresses in predicting nucleosome positioning using biophysical models are reviewed in this paper.