Next-Generation Drugs and Probes for Chromatin Biology: From Targeted Protein Degradation to Phase Separation
Chromatin 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 o...
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-08-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/23/8/1958 |
| _version_ | 1818509503249776640 |
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| author | Katerina Cermakova H. Courtney Hodges |
| author_facet | Katerina Cermakova H. Courtney Hodges |
| author_sort | Katerina Cermakova |
| collection | DOAJ |
| description | Chromatin 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. |
| first_indexed | 2024-12-10T22:46:21Z |
| format | Article |
| id | doaj.art-8e809b095df34652a8dd4e6ab7f924fa |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-10T22:46:21Z |
| publishDate | 2018-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-8e809b095df34652a8dd4e6ab7f924fa2022-12-22T01:30:35ZengMDPI AGMolecules1420-30492018-08-01238195810.3390/molecules23081958molecules23081958Next-Generation Drugs and Probes for Chromatin Biology: From Targeted Protein Degradation to Phase SeparationKaterina Cermakova0H. Courtney Hodges1Department of Molecular & Cellular Biology, Center for Precision Environmental Health, and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USADepartment of Molecular & Cellular Biology, Center for Precision Environmental Health, and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USAChromatin 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.http://www.mdpi.com/1420-3049/23/8/1958degronPROTACVHLcereblonrapamycinFRBFKBPHalo-tagSNAP-tagchemically induced proximity |
| spellingShingle | Katerina Cermakova H. Courtney Hodges Next-Generation Drugs and Probes for Chromatin Biology: From Targeted Protein Degradation to Phase Separation Molecules degron PROTAC VHL cereblon rapamycin FRB FKBP Halo-tag SNAP-tag chemically induced proximity |
| title | Next-Generation Drugs and Probes for Chromatin Biology: From Targeted Protein Degradation to Phase Separation |
| title_full | Next-Generation Drugs and Probes for Chromatin Biology: From Targeted Protein Degradation to Phase Separation |
| title_fullStr | Next-Generation Drugs and Probes for Chromatin Biology: From Targeted Protein Degradation to Phase Separation |
| title_full_unstemmed | Next-Generation Drugs and Probes for Chromatin Biology: From Targeted Protein Degradation to Phase Separation |
| title_short | Next-Generation Drugs and Probes for Chromatin Biology: From Targeted Protein Degradation to Phase Separation |
| title_sort | next generation drugs and probes for chromatin biology from targeted protein degradation to phase separation |
| topic | degron PROTAC VHL cereblon rapamycin FRB FKBP Halo-tag SNAP-tag chemically induced proximity |
| url | http://www.mdpi.com/1420-3049/23/8/1958 |
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