The Functions of BET Proteins in Gene Transcription of Biology and Diseases
| Autor: | Claudia Kim, Ka Lung Cheung, Ming-Ming Zhou |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Regulation of gene expression
BRD4 biology QH301-705.5 bromodomain and extra-terminal domain proteins RNA polymerase II hemic and immune systems Review Biochemistry Genetics and Molecular Biology (miscellaneous) Biochemistry Chromatin remodeling Bromodomain Chromatin Cell biology gene transcription Histone bromodomain inhibitors biology.protein cancer Molecular Biosciences Biology (General) Molecular Biology Transcription factor |
| Zdroj: | Frontiers in Molecular Biosciences, Vol 8 (2021) Frontiers in Molecular Biosciences |
| Popis: | The BET (bromodomain and extra-terminal domain) family proteins, consisting of BRD2, BRD3, BRD4, and testis-specific BRDT, are widely acknowledged as major transcriptional regulators in biology. They are characterized by two tandem bromodomains (BDs) that bind to lysine-acetylated histones and transcription factors, recruit transcription factors and coactivators to target gene sites, and activate RNA polymerase II machinery for transcriptional elongation. Pharmacological inhibition of BET proteins with BD inhibitors has been shown as a promising therapeutic strategy for the treatment of many human diseases including cancer and inflammatory disorders. The recent advances in bromodomain protein biology have further uncovered the complex and versatile functions of BET proteins in the regulation of gene expression in chromatin. In this review article, we highlight our current understanding of BET proteins’ functions in mediating protein–protein interactions required for chromatin-templated gene transcription and splicing, chromatin remodeling, DNA replication, and DNA damage repair. We further discuss context-dependent activator vs. repressor functions of individual BET proteins, isoforms, and bromodomains that may be harnessed for future development of BET bromodomain inhibitors as emerging epigenetic therapies for cancer and inflammatory disorders. |
| Databáze: | OpenAIRE |
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