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© 2014 Wiley-VCH Verlag & Co. KGaA. All rights reserved. Transcription of genes is regulated by a complex network of transcription factors and transcriptional regulators that are recruited to acetylated euchromatin by protein interaction modules of the bromodomain family, a conserved helical domain that specifically recognizes ε{lunate}-N-acetylated lysine residues. This chapter describes the discovery and characterization of inhibitors of the bromo and extra terminal (BET) family, which consists of BRD2, BRD3, BRD4, and BRDT in humans. Evaluation of specific inhibitors targeting the acetyl-lysine site validated the targeting of BET bromodomains in cancer; the chapter discusses the major biological findings that have been elaborated by BET-specific chemical probes. The development of BET-specific inhibitors provides a unique tool for the understanding of gene transcription and potentially new treatment options for aggressive cancers and inflammation. Fluorescence recovery after photobleaching (FRAP) assays demonstrated that BET inhibitors efficiently displace BET transcriptional regulators from chromatin, resulting in tissue-specific changes in gene expression.

Original publication

DOI

10.1002/9783527687503.ch20

Type

Chapter

Book title

Concepts and Case Studies in Chemical Biology

Publication Date

06/10/2014

Pages

295 - 308