Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
Center for Functional Genomics and Tissue Plasticity (ATLAS), University of Southern Denmark, Odense, Denmark.
Methods Mol Biol. 2022;2448:155-175. doi: 10.1007/978-1-0716-2087-8_11.
Transcription factor (TF) networks orchestrate the regulation of gene programs in mammalian cells, including white and brown adipocytes. In this protocol, we outline how genomics and transcriptomics data can be integrated to infer causal TFs of a given cellular response or cell type using "Integrated analysis of Motif Activity and Gene Expression changes of transcription factors" (IMAGE). Here, we show how key regulatory TFs controlling white and brown adipocyte gene programs can be predicted from chromatin accessibility and RNA-seq data. Furthermore, we demonstrate how information about target sites and target genes of the predicted key regulators can be integrated to propose testable hypotheses regarding the role and mechanisms of TFs.
转录因子 (TF) 网络协调哺乳动物细胞中基因程序的调控,包括白色和棕色脂肪细胞。在本方案中,我们概述了如何整合基因组学和转录组学数据,使用“转录因子的基序活性和基因表达变化的综合分析” (IMAGE) 推断给定细胞反应或细胞类型的因果 TF。在这里,我们展示了如何从染色质可及性和 RNA-seq 数据中预测控制白色和棕色脂肪细胞基因程序的关键调节 TF。此外,我们还展示了如何整合关于预测关键调节剂的靶位点和靶基因的信息,以提出关于 TF 的作用和机制的可测试假设。