Targeting Chromatin

Chromatin-associated proteins are emerging as new drug targets for a variety of diseases, especially cancer. This special Focus issue highlights various approaches for ‘targeting chromatin’ for therapeutic intervention.

Misregulation of gene cohorts, which is caused by aberrant chromatin features and is observed in various cancers, has spurred the development and use of epigenetic anti-cancer drugs. Here, we argue that, in addition to small-molecule inhibitors that target chromatin regulators, synthetic reader-effectors that are recruited to abnormal chromatin features have the potential to correct gene misregulation in epigenetic therapy.

Noberini and Bonaldi discuss how mass spectrometry–based technologies aid in identifying the full target spectrum of bioactive molecules.

Tzelepis, Rausch and Kouzarides review the action of RNA modifications in the context of chromatin and discuss the emerging potential of RNA-modifying enzymes as new drug targets.

Arrowsmith and Schapira review recent progress in the discovery of drug-like small molecules that antagonize the function of non-bromodomain chromatin readers.

Zaware and Zhou review the current understanding of bromodomain biology and discuss the latest development of small-molecule inhibitors that target these protein domains as emerging therapies for cancer and inflammatory disorders.

Husmann and Gozani review the biochemical and biological activities of histone lysine methyltransferases and their connections to human diseases, focusing on cancer.