Figure 1.

Schematic representation of the mechanism of action of select histone modifying compounds tested on the lung cancer epigenome. DZNep lowers EZH2 protein levels, decreasing polycomb complex activity and H3K27 methylation. JIB-04 inhibits the enzymatic activity of Jumonji histone demethylases, blocking the demethylation of tri and dimethylated histone lysines and decreasing tumor growth in vivo, while LSD1 inhibitors block the demethylation of monomethylated lysines. JQ1 prevents BRD4 binding to histones at acetylated lysines. HDAC inhibitors prevent the deacetylation of lysines, increasing acetylation and keeping chromatin in a more open, transcriptionally competent conformation.