Transcription Regulation by the Mediator Complex

Nat Rev Mol Cell Biol. 2018 Apr;19(4):262-274. doi: 10.1038/nrm.2017.115. Epub 2017 Dec 6.

Abstract

Alterations in the regulation of gene expression are frequently associated with developmental diseases or cancer. Transcription activation is a key phenomenon in the regulation of gene expression. In all eukaryotes, mediator of RNA polymerase II transcription (Mediator), a large complex with modular organization, is generally required for transcription by RNA polymerase II, and it regulates various steps of this process. The main function of Mediator is to transduce signals from the transcription activators bound to enhancer regions to the transcription machinery, which is assembled at promoters as the preinitiation complex (PIC) to control transcription initiation. Recent functional studies of Mediator with the use of structural biology approaches and functional genomics have revealed new insights into Mediator activity and its regulation during transcription initiation, including how Mediator is recruited to transcription regulatory regions and how it interacts and cooperates with PIC components to assist in PIC assembly. Novel roles of Mediator in the control of gene expression have also been revealed by showing its connection to the nuclear pore and linking Mediator to the regulation of gene positioning in the nuclear space. Clear links between Mediator subunits and disease have also encouraged studies to explore targeting of this complex as a potential therapeutic approach in cancer and fungal infections.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cyclin-Dependent Kinase 8 / antagonists & inhibitors
  • Evolution, Molecular
  • Gene Expression Regulation
  • Humans
  • Mediator Complex / chemistry
  • Mediator Complex / genetics*
  • Mediator Complex / metabolism*
  • Models, Biological
  • Models, Genetic
  • Mycoses / genetics
  • Mycoses / metabolism
  • Mycoses / therapy
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / therapy
  • Nuclear Pore / genetics
  • Nuclear Pore / metabolism
  • RNA Polymerase II / metabolism
  • Regulatory Sequences, Nucleic Acid
  • Signal Transduction
  • Transcription Initiation, Genetic
  • Transcription, Genetic*
  • Transcriptional Activation

Substances

  • Mediator Complex
  • CDK8 protein, human
  • Cyclin-Dependent Kinase 8
  • RNA Polymerase II