ChIP-Seq reveals functional role of p300.

<p>A. EMT marker genes bound by p300 in U87H cells. Shown are genome browser tracks for p300 bound regions near several EMT marker genes, where the horizontal axis represent coordinates along the genome and the height of the solid area represents the number of ChIP-Seq reads mapped to a position in the genome. For each region we show this signal from the ChIP sample that used an antibody specific to p300 (bottom track) and the signal from the sample that used an IgG antibody for non-specific binding (top track). Arrow indicates direction of transcription. B. Regions that are more hypersensitive (HS) in the U87H cells were significantly enriched for overlap with p300 binding regions (p<1E-05) compared to a background of all regions called hypersensitive in U87H cells, for a range of peak calling thresholds of hypersensitivity specified on the x-axis tick marks. Enrichment p-values computed by Fisher exact test are indicated immediately below each set of bars.</p

PCST constructed from the U87 datasets.

<p>This is a composite network representing the union of the optimal solution to the original PCST problem and 10 suboptimal solutions where 15 percent of the nodes must be different from the optimal solution. TF: transcription factor. Node weight: the log2 fold changes in phosphorylation from the phosphoproteomic data comparing U87H to U87DK cells, or values from the expression regression procedure using the mRNA microarray, DNase-Seq and transcription factor motif data. The absolute value of node weights was used as penalty values for the PCST algorithm.</p

High-, mid- lower-ranked nodes by the PCST network and the experiments used to validate their importance.

<p>For cell viability assays, the inhibitors used are listed. Note that some inhibitors have multiple targets. For ChIP-Seq, the antibody used is listed.</p

Validation of targets predicted by network connectivity by cell viability assays.

<p>A. Cell viability for treatment with compounds targeting high-scoring nodes (high-ranked targets), intermediate-scoring nodes (mid-ranked targets) and low-scoring nodes (lower-ranked targets), at 0.5 µM concentration of 17-AAG, 5 µM for harmine (due to low solubility in DMSO) and 10 µM concentration of others. The color bar at the top of each target corresponds to its relative ranking within the interactome. B. Dose response curves of compounds targeting high-scoring nodes and lower-scoring nodes for those that can be fitted to the four-parameter log-logistic model (lack-of-fit test p-value>0.05). P-values between cell lines were computed by comparing the model where one curve was fitted to the data from each cell line to the null model where one shared curve was fitted to the data from both cell lines.</p

Enriched Gene Ontology (GO) categories of p300 target genes in U87H cells.

<p>1,969 genes within 10 kb of 7,657 high stringency peaks called by MACS (p<1E-07) <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002887#pcbi.1002887-Zhang1" target="_blank">[112]</a> were input into the DAVID functional annotation tool <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002887#pcbi.1002887-Yamoutpour1" target="_blank">[120]</a> to identify enriched Biological Process terms with FDR <5%.</p