Key Points
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The control of transcription initiation is a primary mechanism for regulating gene expression, especially in governing developmental and cell-specific programmes of gene expression.
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For much of the past 25 years the model of a largely universal, highly conserved and monolithic core promoter recognition 'pre-initiation complex' composed of general factors that is responsible for initiating transcription in all eukaryotes prevailed.
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Gene and cell-type-specific transcriptional regulation has traditionally been viewed as the role of sequence-specific enhancer and promoter DNA binding activators/repressors.
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New evidence suggests that contrary to the conventional textbook models, there may be major diversification and switching of core promoter recognition complexes during cellular differentiation in eukaryotes.
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Initial evidence for loss of the prototypical transcriptor factor IID (TFIID) and utilization of non-prototypical or orphan TATA-box-binding protein (TBP)-associated factors (TAFs) and TBP-related factors (TRFs) in directing cell-type-specific transcription initiation arose from studies of myogenesis, oogenesis and spermatogenesis.
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TRF2 and TRF3 are highly expressed in germ cells and are important for germ cell differentiation.
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There is a growing body of evidence pointing to novel functions and cell-type-specific activities of different subunits and components of the core transcription machinery.
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Switching of the composition of the core promoter machinery during terminal differentiation of cell types may provide a key mechanism during development of eukaryotes that has evolved to accommodate highly diversified gene expression programmes in multicellular organisms.
Abstract
The eukaryotic core promoter recognition complex was generally thought to play an essential but passive role in the regulation of gene expression. However, recent evidence now indicates that core promoter recognition complexes together with 'non-prototypical' subunits may have a vital regulatory function in driving cell-specific programmes of transcription during development. Furthermore, new roles for components of these complexes have been identified beyond development; for example, in mediating interactions with chromatin and in maintaining active gene expression across cell divisions.
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Acknowledgements
We apologize to those whose relevant research we were unable to discuss owing to space limitations. J.A.G. was funded by Grant R01 GM55235 from the National Institute of General Medical Sciences and R.T. was partly funded by R37 CA25417 from the National Cancer Institute.
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FURTHER INFORMATION
Nature Reviews Genetics series on Modes of transcriptional regulation
Glossary
- RNA polymerase II
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(RNAPII). The enzyme that synthesizes mRNA in eukaryotic cells. RNAPII is composed of 12 protein subunits (RPB1–RPB12). The binding of RNAPII to promoters and the initiation of transcription requires many general transcription factors (TFs), for example, TFIIA, TFIIB, TFIID, TFIIE, TFIIF and TFIIH.
- Core promoter
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The region of a gene to which RNA polymerase II and the general transcription factors (TFs) bind to initiate transcription. Core promoters span from approximately 40 base pairs upstream to 40 base pairs downstream of the transcription start site and are composed of DNA elements to which subunits of TFIID (or TFIIB) bind.
- Pre-initiation complex
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The assembly of general transcription factors and RNA polymerase II on core promoter DNA. This complex, which can be assembled in the absence of nucleotide triphosphates in vitro, is competent to initiate transcription in the presence of nucleotides.
- Transcription factor IID
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(TFIID). A transcription factor for RNA polymerase II that binds core promoters. The TFIID complex is composed of the TATA-box-binding protein (TBP) and 13 or 14 TBP-associated factors.
- TATA-box-binding protein
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(TBP). The central subunit of transcription factor IID. TBP binds TATA boxes found in the core promoters of some eukaryotic mRNA genes.
- TBP-associated factor
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(TAF). All subunits of the transcription factor IID (TFIID) complex other than TATA-box-binding protein (TBP) are TAFs. There are 13 or 14 TAFs in the prototypical TFIID complex. There are also several proteins with sequence similarity to the prototypical TAFs, which are referred to as non-prototypical TAFs.
- Core promoter recognition factor
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A protein or multi-subunit complex that binds with sequence specificity to core promoter elements. The prototypical core promoter recognition factor for mRNA genes in eukaryotes is transcription factor IID, subunits of which recognize multiple core promoter elements.
- TBP-related factor
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(TRF). A protein that is highly related in sequence to TATA-box-binding protein (TBP). Two TRF proteins are discussed in this Review: TRF2 (also known as TLF, TLP, TRP or TBPL1) and TRF3 (also known as TBPL2).
- Mitotic bookmarking
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The process by which genes that are active before mitosis are marked such that transcription begins again at these genes when cells exit mitosis and enter the G1 phase of the cell cycle.
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Goodrich, J., Tjian, R. Unexpected roles for core promoter recognition factors in cell-type-specific transcription and gene regulation. Nat Rev Genet 11, 549–558 (2010). https://doi.org/10.1038/nrg2847
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DOI: https://doi.org/10.1038/nrg2847
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