TFClass: a classification of human transcription factors and their rodent orthologs

Abstract

TFClass aims at classifying eukaryotic transcription factors (TFs) according to their DNA-binding domains (DBDs). For this, a classification schema comprising four generic levels (superclass, class, family and subfamily) was defined that could accommodate all known DNA-binding human TFs. They were assigned to their (sub-)families as instances at two different levels, the corresponding TF genes and individual gene products (protein isoforms). In the present version, all mouse and rat orthologs have been linked to the human TFs, and the mouse orthologs have been arranged in an independent ontology. Many TFs were assigned with typical DNA-binding patterns and positional weight matrices derived from high-throughput in-vitro binding studies. Predicted TF binding sites from human gene upstream sequences are now also attached to each human TF whenever a PWM was available for this factor or one of his paralogs. TFClass is freely available at http://tfclass.bioinf.med.uni-goettingen.de/ through a web interface and for download in OBO format.

C/EBPβ and C/EBPδ transcription factors: Basic biology and roles in the CNS

“…The 17 aa sequence RRERNNIAVRKSRDKAK in the basic DNA binding domain stands out in the alignment of C/EBP sequences because it is fully conserved in C/EBPα, β, δ and ε (human and mouse) ( Figure 6A). This suggests that no differences in binding affinity to a given DNA sequence exist among these C/EBPs and supports the existence of a unique C/EBP consensus sequence (Wingender et al 2015); Figure 6B). Certainly, a given C/EBP site within a promoter may be bound by different C/EBP proteins with different affinities in physiological conditions because of interactions between the C/EBP and other proteins through less conserved domains (N-terminal region or Leu-zipper).…”

“…Data is from http://www.edgar-wingender.de/Class%201.1.html; September 22, 2014 version. (Wingender et al 2015). Note that according to this source, CHOP or C/EBPε cannot form homodimers whereas data by (Newman and Keating 2003) suggest otherwise.…”

“…The bZIP class contains more than 100 members including c-fos, c-jun, CREBs, ATFs or Maf (Wingender et al 2015). All these factors contain a bZIP domain in which the DNA binding domain that allows recognition of specific DNA sequences differs from that of C/EBPs.…”

“…For a more precise sequence of the C/EBP canonical site see (Wingender et al 2015) and for C/EBP-Cre/ATF sites see (Tsukada et al 2011). …”

ZFX acts as a transcriptional activator in multiple types of human tumors by binding downstream from transcription start sites at the majority of CpG island promoters

“…In many cases, the transcriptional dysregulation is driven by altered expression levels or activity of transcription factors (TFs) (Yao et al 2015;Rhie et al 2016). There are about 2000 DNA-binding TFs in the human genome, but little is known about most of these regulators (Vaquerizas et al 2009;Wingender et al 2015). We previously identified distinct sets of TFs having increased expression associated with different cancers (Yao et al 2015;Rhie et al 2016).…”