Abstract
In mammals, transcriptional factors (TFs) drive gene expression by binding to regulatory elements in a cooperative manner. Deciphering the rules of such cooperation is crucial to obtain a full understanding of cellular homeostasis and development. Although this is a long-standing topic, there is no comprehensive database for biologists to access the syntax of TF binding sites. Here we present TFSyntax (https://tfsyntax.zhaopage.com), a database focusing on the arrangement of TF binding sites. TFSyntax maps the binding motif of 1299 human TFs and 890 mouse TFs across 382 cells and tissues, representing the most comprehensive TF binding map to date. In addition to location, TFSyntax defines motif positional preference, density and colocalization within accessible elements. Powered by a series of functional modules based on web interface, users can freely search, browse, analyze, and download data of interest. With comprehensive characterization of TF binding syntax across distinct tissues and cell types, TFSyntax represents a valuable resource and platform for studying the mechanism of transcriptional regulation and exploring how regulatory DNA variants cause disease.