Publication roundup: TRANSFAC


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Publication roundup: TRANSFAC

TRANSFAC is a unique knowledge-base containing published data on eukaryotic transcription factors and miRNAs, their experimentally-proven binding sites, and regulated genes. Here we’ve identified a few papers referencing the use of TRANSFAC.

The handedness-associated PCSK6 locus spans an intronic promoter regulating novel transcripts
Shore et al.

Following up on their previously published GWAS study which looked at genetic signatures of handedness in individuals with dyslexia, the authors performed a detailed analysis of the PCSK6 locus and specifically SNP rs11855145. TRANSFAC was used for in silico analysis of transcription factor binding at this site, predicting an allelic effect on binding of several HOX transcription factors which have been shown to be involved in anterior/posterior developmental patterning. In vitro EMSA confirmed an allelic difference for transcription factor binding site affinity.

Erosion of conserved binding sites in personal genomes points to medical histories
Guturu et al.

The authors of this study used matrices from TRANSFAC to perform an analysis of variants that fall within conserved predicted transcription factor binding sites and are predicted to significantly decrease transcription factor binding affinity compared to the ancestral reference nucleotide. Their work suggests that these variants, which they call conserved binding site eroding loci (CoBELs), tend to congregate near functionally related genes and influence heritable phenotypes providing new insight into disease penetrance.

Antagonistic effects of IL-17 and D-resolvins on endothelial Del-1 expression through a GSK-3β-C/EBPβ pathway
Maekawa et al.

In this study, the authors sought to characterize the mechanism of regulation of Del-1, an endothelial cell-secreted anti-inflammatory protein whose expression is inversely related to IL-17 expression. Based on prior knowledge of IL-17 stimulation resulting in phosphorylation and inactivation of the transcription factor C/EBPβ, coupled with parallel knowledge that IFNγ stimulation simultaneously enhances transcriptional activity of C/EBPβ and increases Del-1 expression, the authors hypothesized that C/EBPβ may in fact be a regulator of Del-1 expression. Promoter analysis of the Del-1 encoding gene (EDIL3) using TRANSFAC identified two predicted binding sites for C/EBPβ. The relevance of these binding sites was confirmed using ChIP-seq data provided within TRANSFAC suggesting that C/EBPβ is indeed a positive regulator of Del-1 expression.

A novel, dynamic pattern-based analysis of NF-κB binding during the priming phase of liver regeneration reveals switch-like functional regulation of target genes
Cook et al.

The authors of this study sought to characterize the role of transcriptional regulation by NF-κB during liver regeneration. They used ChIP-chip analysis to isolate NF-κB binding sites, followed by de novo motif discovery to identify other transcription factors associated with transcriptional regulation during this process. TRANSFAC was used to analyze the de novo motifs, identifying potential co-regulators including AP-1, AP-2, SMAD3, TAL1 and more. Validation of NF-κB targets was performed by ChIP qPCR with primers designed using TRANSFAC.

Activation of the Nrf2 response by intrinsic hepatotoxic drugs correlates with suppression of NF-κB activation and sensitizes toward TNFα-induced cytotoxicity
Herpers et al.

The aim of this study was to better understand Nrf2 and NF-κB signaling in the context of response to drug-induced liver injury. Common sources for protein-protein interaction data were used to assemble the list of genes involved in these two pathways. TRANSFAC was used to uniquely provide the set of genes bound by the terminal NFE2L2 and RELA transcription factors at the end of the respective signaling cascades. The resulting list of genes was analyzed for differential expression upon exposure to compounds associated with drug-induced liver injury.

Read more about TRANSFAC