TY - JOUR A1 - Cheng, Chao A1 - Alexander, Roger A1 - Min, Renqiang A1 - Leng, Jing A1 - Yip, Kevin Y. A1 - Rozowsky, Joel A1 - Yan, Koon-Kiu A1 - Dong, Xianjun A1 - Djebali, Sarah A1 - Ruan, Yijun A1 - Davis, Carrie A. A1 - Carninci, Piero A1 - Lassman, Timo A1 - Gingeras, Thomas R. A1 - Guigó, Roderic A1 - Birney, Ewan A1 - Weng, Zhiping A1 - Snyder, Michael A1 - Gerstein, Mark T1 - Understanding transcriptional regulation by integrative analysis of transcription factor binding data Y1 - 2012/09/01 JF - Genome Research JO - Genome Research SP - 1658 EP - 1667 DO - 10.1101/gr.136838.111 VL - 22 IS - 9 UR - http://genome.cshlp.org/content/22/9/1658.abstract N2 - Statistical models have been used to quantify the relationship between gene expression and transcription factor (TF) binding signals. Here we apply the models to the large-scale data generated by the ENCODE project to study transcriptional regulation by TFs. Our results reveal a notable difference in the prediction accuracy of expression levels of transcription start sites (TSSs) captured by different technologies and RNA extraction protocols. In general, the expression levels of TSSs with high CpG content are more predictable than those with low CpG content. For genes with alternative TSSs, the expression levels of downstream TSSs are more predictable than those of the upstream ones. Different TF categories and specific TFs vary substantially in their contributions to predicting expression. Between two cell lines, the differential expression of TSS can be precisely reflected by the difference of TF-binding signals in a quantitative manner, arguing against the conventional on-and-off model of TF binding. Finally, we explore the relationships between TF-binding signals and other chromatin features such as histone modifications and DNase hypersensitivity for determining expression. The models imply that these features regulate transcription in a highly coordinated manner. ER -