Core regulatory circuitries in defining cancer cell identity across the malignant spectrum
| Autor: | Loukia Tsaprouni, Georgios V. Gkoutos, John A. Williams, Suzanne D. Turner, João D. Pereira, Ricky M Trigg, Leila Jahangiri |
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| Rok vydání: | 2020 |
| Předmět: |
BRD4
Immunology Cell Cycle Proteins Context (language use) Review Review Article Computational biology Biology General Biochemistry Genetics and Molecular Biology Epigenesis Genetic 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Neoplasms Gene expression medicine Humans liquid and solid cancers Cell Lineage Gene Regulatory Networks core regulatory circuitry lcsh:QH301-705.5 Transcription factor 030304 developmental biology 0303 health sciences General Neuroscience super-enhancers Cancer medicine.disease Chromatin digestive system diseases Gene Expression Regulation Neoplastic Enhancer Elements Genetic lcsh:Biology (General) Drug development 030220 oncology & carcinogenesis Cancer cell cell identity Protein Binding Transcription Factors |
| Zdroj: | Open Biology, Vol 10, Iss 7 (2020) Open Biology |
| ISSN: | 2046-2441 |
| DOI: | 10.1098/rsob.200121 |
| Popis: | Gene expression programmes driving cell identity are established by tightly regulated transcription factors that auto- and cross-regulate in a feed-forward manner, forming core regulatory circuitries (CRCs). CRC transcription factors create and engage super-enhancers by recruiting acetylation writers depositing permissive H3K27ac chromatin marks. These super-enhancers are largely associated with BET proteins, including BRD4, that influence higher-order chromatin structure. The orchestration of these events triggers accessibility of RNA polymerase machinery and the imposition of lineage-specific gene expression. In cancers, CRCs drive cell identity by superimposing developmental programmes on a background of genetic alterations. Further, the establishment and maintenance of oncogenic states are reliant on CRCs that drive factors involved in tumour development. Hence, the molecular dissection of CRC components driving cell identity and cancer state can contribute to elucidating mechanisms of diversion from pre-determined developmental programmes and highlight cancer dependencies. These insights can provide valuable opportunities for identifying and re-purposing drug targets. In this article, we review the current understanding of CRCs across solid and liquid malignancies and avenues of investigation for drug development efforts. We also review techniques used to understand CRCs and elaborate the indication of discussed CRC transcription factors in the wider context of cancer CRC models. |
| Databáze: | OpenAIRE |
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