Recent progress has firmly established that disregulation of homeostasis and disease (leading to diseases such as cancer) can result from alterations in DNA architecture (epigenetics). A key architectural component of DNA is the winding of the double helix around histone proteins with each segment forming a nucleosome. The amino acids that comprise each histone protein can be modified, for example, by acetylation of lysine amino groups. These acetyl “marks” can serve as recognition points for epigenetic reader proteins which, in turn, serve as recruitment factors to initiate gene transcription. Because of their reversibility and regulation, the lysine acetylation and other epigenetic factors are highly attractive as drug targets. Our team at Epigenetix continues to develop potent, safe inhibitors of the class of reader proteins.