Laboratory of Computational Genomics, Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Laboratory of Genome Structure and Function, Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Methods. 2021 Mar;187:44-53. doi: 10.1016/j.ymeth.2020.03.005. Epub 2020 Mar 30.
Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is a central method in epigenomic research. Genome-wide analysis of histone modifications, such as enhancer analysis and genome-wide chromatin state annotation, enables systematic analysis of how the epigenomic landscape contributes to cell identity, development, lineage specification, and disease. In this review, we first present a typical ChIP-seq analysis workflow, from quality assessment to chromatin-state annotation. We focus on practical, rather than theoretical, approaches for biological studies. Next, we outline various advanced ChIP-seq applications and introduce several state-of-the-art methods, including prediction of gene expression level and chromatin loops from epigenome data and data imputation. Finally, we discuss recently developed single-cell ChIP-seq analysis methodologies that elucidate the cellular diversity within complex tissues and cancers.
染色质免疫沉淀测序（ChIP-seq）是表观基因组学研究的核心方法。对组蛋白修饰（如增强子分析和全基因组染色质状态注释）的全基因组分析，能够系统地分析表观基因组景观如何有助于细胞身份、发育、谱系特化和疾病。在这篇综述中，我们首先介绍了一个典型的 ChIP-seq 分析工作流程，从质量评估到染色质状态注释。我们专注于生物学研究中的实用而非理论方法。接下来，我们概述了各种先进的 ChIP-seq 应用，并介绍了几种最新的方法，包括从表观基因组数据预测基因表达水平和染色质环以及数据插补。最后，我们讨论了最近开发的单细胞 ChIP-seq 分析方法，这些方法阐明了复杂组织和癌症中的细胞多样性。
