Key Points
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Expression of target genes in response to extracellular stimuli is activated by means that include activation of RNA polymerase II (Pol II)-dependent transcription.
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Multiple processes during the early stages of Pol II-dependent transcription are subject to regulation and can therefore function as the rate-limiting step during activation of target genes.
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Activator-dependent recruitment of Pol II and the general transcription factors is essential for high levels of transcription at inducible genes. This process must occur at all induced genes before activation, whether or not recruitment of polymerase is rate-limiting with regards to activation.
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The kinetics of Pol II recruitment and transcription initiation can be stimulated by nucleosome-remodelling complexes that use the energy from ATP hydrolysis to move or displace histones from DNA.
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Co-activators are essential for activator-dependent recruitment of Pol II and the general transcription factors. Mediator and the histone acetyltransferase complex SAGA are well-characterized examples of co-activators.
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Transcription can be regulated at steps that occur after the recruitment of Pol II. These steps include the release of Pol II from a paused state close to the promoter into active transcription elongation in the coding region of the gene.
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The rate-limiting step of transcription can differ between various inducible genes.
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Signalling kinases such as MAPKs sometimes localize to the promoters of target genes at which they can function as transcriptional activators, rapidly facilitating the switch between activated and repressed states of gene expression.
Abstract
The rapid activation of gene expression in response to stimuli occurs largely through the regulation of RNA polymerase II-dependent transcription. In this Review, we discuss events that occur during the transcription cycle in eukaryotes that are important for the rapid and specific activation of gene expression in response to external stimuli. In addition to regulated recruitment of the transcription machinery to the promoter, it has now been shown that control steps can include chromatin remodelling and the release of paused polymerase. Recent work suggests that some components of signal transduction cascades also play an integral part in activating transcription at target genes.
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Acknowledgements
We thank J.Conaway, C. Sato and S. Sato for helpful discussions regarding Mediator composition, and K. Lee and S. Venkatesh for comments on the manuscript.
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Supplementary Figure/Table 1
Complexes involved in inducible gene expression are conserved from yeast to humans. (PDF 844 kb)
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Glossary
- Chromatin
-
A nucleoprotein structure formed of repeating nucleosomal units in which 147 base pairs of DNA are wrapped around an octamer of histone proteins consisting of an H3–H4 tetramer flanked by two H2A–H2B dimers
- Co-activator
-
A protein that is recruited to promoters through interactions with transcriptional activators, and facilitates transcriptional activation through the recruitment of RNA polymerase II and the general transcription factors. Many co-activators also catalyse chromatin modifications that assist the kinetics of recruitment of the general transcription machinery.
- General transcription machinery
-
RNA polymerase II together with the general transcription factors TFIIA, TFIIB, TFIID, TFIIE, TFIIF and TFIIH.
- Transcriptional activator
-
A sequence-specific DNA-binding protein that increases the rate of transcription by recruiting RNA polymerase II, either directly in prokaryotes or through co-activators in eukaryotes.
- Pre-initiation complex
-
A 44 polypeptide complex, which consists of RNA polymerase II and the general transcription factors TFIIA, TFIIB, TFIID, TFIIE, TFIIF and TFIIH. Its formation at TATA-containing core promoters is nucleated by binding of TATA-binding protein (a component of TFIID) to the TATA element in the promoter DNA sequence.
- Acidic activation domain
-
The type of transactivation domain found in transcriptional activators such as Gal4. This domain contains a stretch of acidic amino acids and is required for interactions with co-activators.
- ATP-dependent nucleosome-remodelling complex
-
A transcriptional regulatory complex that uses the energy obtained from ATP hydrolysis to move or displace histone octamers from DNA.
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Weake, V., Workman, J. Inducible gene expression: diverse regulatory mechanisms. Nat Rev Genet 11, 426–437 (2010). https://doi.org/10.1038/nrg2781
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DOI: https://doi.org/10.1038/nrg2781
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