Next-Generation Drugs and Probes for Chromatin Biology: From Targeted Protein Degradation to Phase Separation
AbstractChromatin regulation is a critical aspect of nuclear function. Recent advances have provided detailed information about dynamic three-dimensional organization of chromatin and its regulatory factors. Mechanisms crucial for normal nuclear function and epigenetic control include compartmentalization of biochemical reactions by liquid-phase separated condensates and signal-dependent regulation of protein stability. Synthetic control of these phenomena by small molecules provides deep insight into essential activities such as histone modification, BAF (SWI/SNF) and PBAF remodeling, Polycomb repression, enhancer looping by cohesin and CTCF, as well as many other processes that contribute to transcription. As a result, a complete understanding of the spatiotemporal mechanisms that underlie chromatin regulation increasingly requires the use of fast-acting drugs and chemical probes. Here, we provide a comprehensive review of next-generation chemical biology tools to interrogate the chromatin regulatory landscape, including selective PROTAC E3 ubiquitin ligase degraders, degrons, fluorescent ligands, dimerizers, inhibitors, and other drugs. These small molecules provide important insights into the mechanisms that govern gene regulation, DNA repair, development, and diseases like cancer. View Full-Text
Share & Cite This Article
Cermakova, K.; Hodges, H.C. Next-Generation Drugs and Probes for Chromatin Biology: From Targeted Protein Degradation to Phase Separation. Molecules 2018, 23, 1958.
Cermakova K, Hodges HC. Next-Generation Drugs and Probes for Chromatin Biology: From Targeted Protein Degradation to Phase Separation. Molecules. 2018; 23(8):1958.Chicago/Turabian Style
Cermakova, Katerina; Hodges, H. C. 2018. "Next-Generation Drugs and Probes for Chromatin Biology: From Targeted Protein Degradation to Phase Separation." Molecules 23, no. 8: 1958.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.