Zhu Lihua Julie
Program in Gene Function and Expression, University of Massachusetts - Medical School, Worcester, MA, USA.
Methods Mol Biol. 2013;1067:105-24. doi: 10.1007/978-1-62703-607-8_8.
Epigenetic regulation and interactions between transcription factors and regulatory genomic regions play crucial roles in controlling transcriptional regulatory networks that drive development, environmental responses, and disease. Chromatin immunoprecipitation (ChIP) followed by high-throughput sequencing (ChIP-seq) and ChIP followed by genomic tiling microarray hybridization (ChIP-chip) are the two of the most widely used technologies for genome-wide identification of DNA protein interactions and histone modification in vivo. Many algorithms and tools have been developed and evaluated that allow identification of transcription factor binding sites from ChIP-seq or ChIP-chip datasets. However, binding site identification is only the first step; the ultimate goal is to discover the regulatory network of the transcription factor (TF). Here, we present a common workflow for downstream analysis of ChIP-chip and ChIP-seq with an emphasis on annotating binding sites and integration with gene expression data to identify direct and indirect targets of the TF. These tools will help with the overall goal of unraveling transcriptional regulatory networks using datasets publicly available in GEO.
表观遗传调控以及转录因子与调控基因组区域之间的相互作用，在控制驱动发育、环境响应和疾病的转录调控网络中起着关键作用。染色质免疫沉淀（ChIP）结合高通量测序（ChIP-seq）以及染色质免疫沉淀结合基因组平铺微阵列杂交（ChIP-chip），是在全基因组范围内鉴定体内DNA与蛋白质相互作用以及组蛋白修饰最广泛使用的两种技术。已经开发并评估了许多算法和工具，可从ChIP-seq或ChIP-chip数据集中识别转录因子结合位点。然而，结合位点识别仅仅是第一步；最终目标是发现转录因子（TF）的调控网络。在此，我们提出了一个用于ChIP-chip和ChIP-seq下游分析的通用工作流程，重点在于注释结合位点并与基因表达数据整合，以识别TF的直接和间接靶标。这些工具将有助于实现利用GEO中公开可用的数据集阐明转录调控网络的总体目标。
