Figure 5. Correspondence of chromatin state changes with RNA expression changes during transition to tumorigenesis.

(A) Scatter plot comparing gene expression values [log₂ (FPKM+1)] in NTM_H and TM_H for RefSeq genes. (B) Relative enrichment of chromatin state transitions at promoters of down-regulated genes compared to up-regulated genes (left panel) or up-regulated genes promoters compared to down-regulated (right panel) for all pairs of chromatin state transitions. Red shows enrichment whereas blue is depletion. (C) Scatter plot comparing promoter acetylations [log₂(RPKM+1)] around +/-2kb of each RefSeq gene in NTM_H and TM_H. The line in red is a regression line, while in black is the y=x line. (D) Scatter plot displays directional log₁₀(p-value) for acetylation and gene expression changes between TM_H and NTM_H. Negative values represent genes with decreased expression or acetylation levels in TM_H compared to NTM_H cells. Dashed lines show the significance cut-off for acetylation or expression changes. Genes with significant gene expression and/or acetylation changes are colored based on grouping indicated. (E) Heat map represents enriched pathways (pathway commons) for each group identified in Figure 5D. Color scale represents –log₁₀(HyperFdrQ corrected). (F) UCSC genome browser view of average acetylation and RNA-Seq for an example from each of the LossAc_LossExp (DUSP5) (top) and LossAc_ConstExp (ATM) groups (bottom). (G) Graph showing relative levels of DUSP5 in NTM_H cells harboring either control or DUSP5 shRNAs. (H) Western blot showing levels of p-ERK in NTM_H cells harboring either control or DUSP5 shRNAs. (I) Growth curve showing proliferative capacity of NTM_H cells harboring control or DUSP5 shRNAs (shDUSP5-1 and shDUSP5-2). See also Figure S6 and Table S7.