School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane 4072, Australia.
Department of Pharmacology, University of Nevada School of Medicine, Reno, NV 89557-0357, USA.
Nucleic Acids Res. 2017 Feb 28;45(4):e19. doi: 10.1093/nar/gkw956.
Identifying the genomic regions and regulatory factors that control the transcription of genes is an important, unsolved problem. The current method of choice predicts transcription factor (TF) binding sites using chromatin immunoprecipitation followed by sequencing (ChIP-seq), and then links the binding sites to putative target genes solely on the basis of the genomic distance between them. Evidence from chromatin conformation capture experiments shows that this approach is inadequate due to long-distance regulation via chromatin looping. We present CisMapper, which predicts the regulatory targets of a TF using the correlation between a histone mark at the TF's bound sites and the expression of each gene across a panel of tissues. Using both chromatin conformation capture and differential expression data, we show that CisMapper is more accurate at predicting the target genes of a TF than the distance-based approaches currently used, and is particularly advantageous for predicting the long-range regulatory interactions typical of tissue-specific gene expression. CisMapper also predicts which TF binding sites regulate a given gene more accurately than using genomic distance. Unlike distance-based methods, CisMapper can predict which transcription start site of a gene is regulated by a particular binding site of the TF.
确定控制基因转录的基因组区域和调控因子是一个重要且尚未解决的问题。目前的首选方法是使用染色质免疫沉淀 followed by sequencing (ChIP-seq) 来预测转录因子 (TF) 的结合位点，然后仅根据它们之间的基因组距离将结合位点与假定的靶基因联系起来。染色质构象捕获实验的证据表明，由于通过染色质环化进行远距离调控，这种方法是不充分的。我们提出了 CisMapper，它使用 TF 结合位点处的组蛋白标记与跨组织面板中每个基因的表达之间的相关性来预测 TF 的调控靶标。使用染色质构象捕获和差异表达数据，我们表明 CisMapper 在预测 TF 的靶基因方面比目前使用的基于距离的方法更准确，并且特别有利于预测组织特异性基因表达中典型的长距离调控相互作用。CisMapper 还比使用基因组距离更准确地预测哪些 TF 结合位点调节给定基因。与基于距离的方法不同，CisMapper 可以预测特定 TF 结合位点调节给定基因的哪个转录起始位点。
