The BET family in immunity and disease

Innate immunity serves as the rapid and first-line defense against invading pathogens, and this process can be regulated at various levels, including epigenetic mechanisms. The bromodomain and extraterminal domain (BET) family of proteins consists of four conserved mammalian members (BRD2, BRD3, BRD...

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Bibliographic Details
Published in:Signal transduction and targeted therapy 2021-01, Vol.6 (1), p.23-23, Article 23
Main Authors: Wang, Nian, Wu, Runliu, Tang, Daolin, Kang, Rui
Format: Article
Language:English
Subjects:
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692/699
Animals
Cancer Research
Cell Biology
Chromatin - immunology
Epigenesis, Genetic - immunology
Humans
Immunity (Disease)
Immunity, Innate
Internal Medicine
Medicine
Medicine & Public Health
Oncology
Pathology
Review
Review Article
RNA polymerase
Transcription Factors - immunology
Transcription, Genetic - immunology
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Summary:Innate immunity serves as the rapid and first-line defense against invading pathogens, and this process can be regulated at various levels, including epigenetic mechanisms. The bromodomain and extraterminal domain (BET) family of proteins consists of four conserved mammalian members (BRD2, BRD3, BRD4, and BRDT) that regulate the expression of many immunity-associated genes and pathways. In particular, in response to infection and sterile inflammation, abnormally expressed or dysfunctional BETs are involved in the activation of pattern recognition receptor (e.g., TLR, NLR, and CGAS) pathways, thereby linking chromatin machinery to innate immunity under disease or pathological conditions. Mechanistically, the BET family controls the transcription of a wide range of proinflammatory and immunoregulatory genes by recognizing acetylated histones (mainly H3 and H4) and recruiting transcription factors (e.g., RELA) and transcription elongation complex (e.g., P-TEFb) to the chromatin, thereby promoting the phosphorylation of RNA polymerase II and subsequent transcription initiation and elongation. This review covers the accumulating data about the roles of the BET family in innate immunity, and discusses the attractive prospect of manipulating the BET family as a new treatment for disease.
ISSN:2059-3635
2095-9907
2059-3635
DOI:10.1038/s41392-020-00384-4