The exploitation of FRET probes to track bromodomain/histone interactions in cells for bromodomain inhibitors.

Abstract

Bromodomain-containing proteins are epigenetic readers of histone codes, which recognize acetylated histones and are involved in transcription, nucleosome remodeling and DNA repair. Chromosomal translocations of bromodomain-containing proteins have been implicated in many diseases. In this regard, small molecules that inhibit bromodomains are promising as therapeutic agents. A fluorescence microscopy-based approach provides information on bromodomain inhibitors that abrogate the interaction between acetylated histones and bromodomains in living cells. We have developed genetically encoded fluorescent probes for histone acetylation called Histacs. We review how these recently developed probes can serve as useful tools to evaluate the intracellular activity of bromodomain inhibitors.

• Authors: Kazuki Sasaki, Minoru Yoshida
• Journal: Drug discovery today. Technologies (Drug Discov Today Technol) Vol. 19 Pg. 51-56 (Mar 2016) ISSN: 1740-6749 [Electronic] England
• PMID: 27769358 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemical References

• Fluorescent Dyes
• Histone Deacetylase Inhibitors
• Histones
• Nuclear Proteins
• Transcription Factors

Topics

• Acetylation
• Animals
• Fluorescence Resonance Energy Transfer
• Fluorescent Dyes (pharmacology)
• Histone Code
• Histone Deacetylase Inhibitors (pharmacology, therapeutic use)
• Histones (metabolism)
• Humans
• Nuclear Proteins (antagonists & inhibitors, metabolism)
• Protein Domains
• Transcription Factors (antagonists & inhibitors, metabolism)