TFClass: an expandable hierarchical classification of human transcription factors

Abstract

TFClass (http://tfclass.bioinf.med.uni-goettingen.de/) provides a comprehensive classification of human transcription factors based on their DNA-binding domains. Transcription factors constitute a large functional family of proteins directly regulating the activity of genes. Most of them are sequence-specific DNA-binding proteins, thus reading out the information encoded in cis-regulatory DNA elements of promoters, enhancers and other regulatory regions of a genome. TFClass is a database that classifies human transcription factors by a six-level classification schema, four of which are abstractions according to different criteria, while the fifth level represents TF genes and the sixth individual gene products. Altogether, nine superclasses have been identified, comprising 40 classes and 111 families. Counted by genes, 1558 human TFs have been classified so far or >2900 different TFs when including their isoforms generated by alternative splicing or protein processing events. With this classification, we hope to provide a basis for deciphering protein-DNA recognition codes; moreover, it can be used for constructing expanded transcriptional networks by inferring additional TF-target gene relations.

Figure 1.

Relative sizes of human TF superclasses. The distribution of TF genera among the 10 superclasses, with the percentages indicated.

Figure 2.

TFClass web interface. In the box on the left, the classification tree is shown and can be expanded by clicking on the individual items. In the example shown, the tree has been automatically expanded around the searched item (CREB-A, see ‘Search’ box in the top right part), and is cut after subfamily 1.1.7.2. The tree can also be browsed by expanding it down to any level (see area labeled ‘Expand to’). Under the tab ‘Details’ on the right, additional information about the active item is displayed directly or as link. Under the tab ‘Protein expression’, tissue specificities of the highlighted factor would be shown. On top, the ‘Search’ box enables to retrieve specific objects and open the tree on the left around the found items.