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.

Mediator subunit MED25 links the jasmonate receptor to transcriptionally active chromatin

“…Thus, the plant MED25 and its animal counterpart cooperate with similar epigenetic regulators in distinct signaling pathways. Animal Mediator was first biochemically isolated as a thyroid hormone receptor-associated protein (TRAP) complex (47), and has been shown to be an indispensable NR-interacting coactivator (26,28,29,47). These previous observations, together with our findings, support a scenario in which plants and animals have evolved distinct, but nonetheless largely similar, mechanisms for NR activation at the level of transcriptional regulation.…”

“…First, the overall protein domain composition of the plant MED25 is largely similar to that of its animal counterpart (19,21). Second, in addition to interacting with MYC2, the plant MED25 interacts with the JA-Ile receptor protein COI1; in an analogous manner, the human MED25 engages in a liganddependent interaction with retinoic acid receptor (RAR) and several other NRs, which are themselves transcription factors (26,28,29,47). Thus, in term of their interaction with MED25, the JA-Ile coreceptor complex (SCF COI1 -JAZs), together with the master transcription factor MYC2, resembles the NR system of metazoans (26,28,29,47).…”

“…Second, in addition to interacting with MYC2, the plant MED25 interacts with the JA-Ile receptor protein COI1; in an analogous manner, the human MED25 engages in a liganddependent interaction with retinoic acid receptor (RAR) and several other NRs, which are themselves transcription factors (26,28,29,47). Thus, in term of their interaction with MED25, the JA-Ile coreceptor complex (SCF COI1 -JAZs), together with the master transcription factor MYC2, resembles the NR system of metazoans (26,28,29,47). Third, we show here that the plant MED25 cooperates with HAC1, an Arabidopsis ortholog of the well-studied animal histone acetyltransferase CBP, for JA-Iletriggered activation of MYC2; in a similar manner, the animal MED25 also cooperates with CBP for RAR activation (48).…”

“…Among the COI1-interacting proteins we identified was the MED25 subunit of Arabidopsis Mediator (19)(20)(21)(22), an evolutionarily conserved multisubunit coregulatory complex whose activity is essential for Pol II-dependent transcription in eukaryotic cells (23)(24)(25)(26)(27)(28)(29).…”

Differential co-expression network analysis for identification of functional modules in HIV infection and tubercolosis-HIV co-infection

“…enhancer-driven) for activated RNAP II transcription. 29,30 The role of some Mediator complex subunits in HIV replication has been attributed to a role on viral transcription, due to its RNAP II-related function or its link to the Tat-mediated transcription through the HIV long terminal repeat. 27,31 For instance, H2 contained several genes associated with mediator complex such as MED13L, MED13, MED9, and MED30.…”