6 research outputs found
Experimental Infection of Conventional Pigs with Streptococcus suis serotype 2 by Aerosolic Exposure
Functional transcription factor target discovery via compendia of binding and expression profiles
Genome-wide experiments to map the DNA-binding locations of
transcription-associated factors (TFs) have shown that the number of genes
bound by a TF far exceeds the number of possible direct target genes.
Distinguishing functional from non-functional binding is therefore a major
challenge in the study of transcriptional regulation. We hypothesized that
functional targets can be discovered by correlating binding and expression
profiles across multiple experimental conditions. To test this hypothesis, we
obtained ChIP-seq and RNA-seq data from matching cell types from the human
ENCODE resource, considered promoter-proximal and distal cumulative regulatory
models to map binding sites to genes, and used a combination of linear and
non-linear measures to correlate binding and expression data. We found that a
high degree of correlation between a gene's TF-binding and expression profiles
was significantly more predictive of the gene being differentially expressed
upon knockdown of that TF, compared to using binding sites in the cell type of
interest only. Remarkably, TF targets predicted from correlation across a
compendium of cell types were also predictive of functional targets in other
cell types. Finally, correlation across a time course of ChIP-seq and RNA-seq
experiments was also predictive of functional TF targets in that tissue.Comment: 15 pages + 8 pages supplementary material; 6 figures, 6 supplementary
figures, 5 supplementary table