Abstract
Bromodomain protein 4 (BRD4) is a transcriptional and epigenetic regulator that plays a pivotal role in cancer and inflammatory diseases. BRD4 binds and stays associated with chromatin during mitosis, bookmarking early G1 genes and reactivating transcription after mitotic silencing. BRD4 plays an important role in transcription, both as a passive scaffold via its recruitment of vital transcription factors and as an active kinase that phosphorylates RNA polymerase II, directly and indirectly regulating transcription. Through its HAT activity, BRD4 contributes to the maintenance of chromatin structure and nucleosome clearance. This review summarizes the known functions of BRD4 and proposes a model in which BRD4 actively coordinates chromatin structure and transcription.
Keywords:
BRD4; Pol II; acetyltransferase; kinase; nucleosome eviction.
© Society for Leukocyte Biology.
MeSH terms
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Acetylation
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Cell Cycle / physiology
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Cell Cycle Proteins
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Cell Differentiation
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Chromatin / metabolism
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Chromatin / ultrastructure
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Gene Expression Regulation, Developmental
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Histone Acetyltransferases / metabolism
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Humans
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Models, Genetic
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Neoplasm Proteins / chemistry
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Neoplasm Proteins / physiology
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Nuclear Proteins / chemistry
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Nuclear Proteins / physiology*
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Nucleosomes / metabolism
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Nucleosomes / ultrastructure
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Oncogene Proteins, Fusion / physiology
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Phosphorylation
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Protein Domains
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Protein Processing, Post-Translational
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RNA Polymerase II / metabolism
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Structure-Activity Relationship
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Transcription Factors / chemistry
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Transcription Factors / metabolism
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Transcription Factors / physiology*
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Transcription, Genetic / physiology*
Substances
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BRD4 protein, human
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BRD4-NUT fusion oncogene protein, human
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Brd4 protein, mouse
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Cell Cycle Proteins
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Chromatin
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Neoplasm Proteins
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Nuclear Proteins
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Nucleosomes
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Oncogene Proteins, Fusion
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Transcription Factors
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Histone Acetyltransferases
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RNA Polymerase II