4-Acyl pyrroles: mimicking acetylated lysines in histone code reading

24.11.2013

Lucas X, Wohlwend D, Hügle M, Schmidtkunz K, Gerhardt S, Schüle R, Jung M, Einsle O, Günther S.

Angew Chem Int Ed Engl. 2013;52(52):14055-9

Angew Chem Int Ed Engl           online article

Chromatin remodeling is a key epigenetic mechanism of gene expression regulation controlled through the posttranscrip- tional modification of histones. Several enzymes, including histone deacetylases and lysine methyltransferases, add or remove functional groups at a variety of residues on histone tails. The recognition of this histone code by “reader” proteins, such as bromodomains (BRDs) and tudor domains, has a critical impact in the regulation of gene expression. Here we have identified a new class of inhibitors for the BET family bromodomain BRD4 that promise to have a broad potential in future drug development approaches.