The Mediator complex and transcription regulation

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.

• CDK8-Mediator
• Gdown1
• gene expression
• paused pol II
• review
• super elongation complex
• TFIIS

Acknowledgements

We thank Francisco Asturias for helpful comments on the manuscript and for providing EM images of yeast Mediator, CKM-Mediator and the CKM. We thank Yuan He and Eva Nogales for assistance with the PIC model figure.

Declaration of interest

Recent work in the Taatjes lab has been supported by the NCI (CA127364; CA175849; CA170741), the American Cancer Society (RSG0927401DMC), and the NSF (MCB-1244175). The authors declare no conflict of interest.