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The Mediator complex and transcription regulation.

Poss ZC, Ebmeier CC, Taatjes DJ - Crit. Rev. Biochem. Mol. Biol. (2013)

Bottom Line: Thus, Mediator is essential for converting biological inputs (communicated by TFs) to physiological responses (via changes in gene expression).We focus on the basics that underlie Mediator function, such as its structure and subunit composition, and describe its broad regulatory influence on gene expression, ranging from chromatin architecture to transcription initiation and elongation, to mRNA processing.We also describe factors that influence Mediator structure and activity, including TFs, non-coding RNAs and the CDK8 module.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry, University of Colorado , Boulder, CO , USA.

ABSTRACT
The Mediator complex is a multi-subunit assembly that appears to be required for regulating expression of most RNA polymerase II (pol II) transcripts, which include protein-coding and most non-coding RNA genes. Mediator and pol II function within the pre-initiation complex (PIC), which consists of Mediator, pol II, TFIIA, TFIIB, TFIID, TFIIE, TFIIF and TFIIH and is approximately 4.0 MDa in size. Mediator serves as a central scaffold within the PIC and helps regulate pol II activity in ways that remain poorly understood. Mediator is also generally targeted by sequence-specific, DNA-binding transcription factors (TFs) that work to control gene expression programs in response to developmental or environmental cues. At a basic level, Mediator functions by relaying signals from TFs directly to the pol II enzyme, thereby facilitating TF-dependent regulation of gene expression. Thus, Mediator is essential for converting biological inputs (communicated by TFs) to physiological responses (via changes in gene expression). In this review, we summarize an expansive body of research on the Mediator complex, with an emphasis on yeast and mammalian complexes. We focus on the basics that underlie Mediator function, such as its structure and subunit composition, and describe its broad regulatory influence on gene expression, ranging from chromatin architecture to transcription initiation and elongation, to mRNA processing. We also describe factors that influence Mediator structure and activity, including TFs, non-coding RNAs and the CDK8 module.

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Evolutionary timeline. Note large intervals for evolution of microbial to eukaryotic life, and for single-celled eukaryotes to metazoans. (see colour version of this figure online at www.informahealthcare.com/bmg).
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f1: Evolutionary timeline. Note large intervals for evolution of microbial to eukaryotic life, and for single-celled eukaryotes to metazoans. (see colour version of this figure online at www.informahealthcare.com/bmg).

Mentions: Mediator is not required for transcription per se, and over evolutionary time (Figure 1), it emerged in eukaryotic organisms. Throughout evolution, Mediator sequences have diverged rapidly, such that identity or similarity is modest between yeast and human subunits (Boube et al., 2002; Bourbon, 2008; Levine & Tjian, 2003). Moreover, human Mediator contains subunits with no identifiable counterpart in yeast (Table 1).Figure 1.


The Mediator complex and transcription regulation.

Poss ZC, Ebmeier CC, Taatjes DJ - Crit. Rev. Biochem. Mol. Biol. (2013)

Evolutionary timeline. Note large intervals for evolution of microbial to eukaryotic life, and for single-celled eukaryotes to metazoans. (see colour version of this figure online at www.informahealthcare.com/bmg).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3852498&req=5

f1: Evolutionary timeline. Note large intervals for evolution of microbial to eukaryotic life, and for single-celled eukaryotes to metazoans. (see colour version of this figure online at www.informahealthcare.com/bmg).
Mentions: Mediator is not required for transcription per se, and over evolutionary time (Figure 1), it emerged in eukaryotic organisms. Throughout evolution, Mediator sequences have diverged rapidly, such that identity or similarity is modest between yeast and human subunits (Boube et al., 2002; Bourbon, 2008; Levine & Tjian, 2003). Moreover, human Mediator contains subunits with no identifiable counterpart in yeast (Table 1).Figure 1.

Bottom Line: Thus, Mediator is essential for converting biological inputs (communicated by TFs) to physiological responses (via changes in gene expression).We focus on the basics that underlie Mediator function, such as its structure and subunit composition, and describe its broad regulatory influence on gene expression, ranging from chromatin architecture to transcription initiation and elongation, to mRNA processing.We also describe factors that influence Mediator structure and activity, including TFs, non-coding RNAs and the CDK8 module.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry, University of Colorado , Boulder, CO , USA.

ABSTRACT
The Mediator complex is a multi-subunit assembly that appears to be required for regulating expression of most RNA polymerase II (pol II) transcripts, which include protein-coding and most non-coding RNA genes. Mediator and pol II function within the pre-initiation complex (PIC), which consists of Mediator, pol II, TFIIA, TFIIB, TFIID, TFIIE, TFIIF and TFIIH and is approximately 4.0 MDa in size. Mediator serves as a central scaffold within the PIC and helps regulate pol II activity in ways that remain poorly understood. Mediator is also generally targeted by sequence-specific, DNA-binding transcription factors (TFs) that work to control gene expression programs in response to developmental or environmental cues. At a basic level, Mediator functions by relaying signals from TFs directly to the pol II enzyme, thereby facilitating TF-dependent regulation of gene expression. Thus, Mediator is essential for converting biological inputs (communicated by TFs) to physiological responses (via changes in gene expression). In this review, we summarize an expansive body of research on the Mediator complex, with an emphasis on yeast and mammalian complexes. We focus on the basics that underlie Mediator function, such as its structure and subunit composition, and describe its broad regulatory influence on gene expression, ranging from chromatin architecture to transcription initiation and elongation, to mRNA processing. We also describe factors that influence Mediator structure and activity, including TFs, non-coding RNAs and the CDK8 module.

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