Mediator, a transcriptional coactivator complex, is essential for transcription but is not a required component of a functional preinitiation complex, indicating that Mediator is not equivalent to a general transcription factor.

Detailed molecular profiling investigations alongside antitumor testing and tolerability studies in animals suggest caution when considering the clinical development of inhibitors of CDK8 and CDK19, since a clear therapeutic window could not be demonstrated with two structurally distinct, potent and selective prototype drugs.

Integrative modeling of results from chemical cross-linking, electron microscopy, and homology modeling yield a three-dimensional model of the entire Mediator complex in yeast.

The TPL corepressor binds to the core mediator complex through MED21 to inhibit transcription while simultaneously priming repressed genes for rapid reactivation.

Genome-wide recruitment of Mediator and Pol II is reduced in yeast lacking the Med2-Med3-Med15 tail module triad, and Mediator association with gene promoters depends on Pol II, Taf1, and TBP.

Transcriptional activation domains achieve rapid, dynamic, specific interaction with Mediator through binding of an unstructured peptide to multiple hydrophobic surfaces without particular amino acid side chain interactions.

The ZF-CxxC protein FBXL19 recruits kinase-associated Mediator to CpG islands of silent developmental genes in embryonic stem cells, which primes these genes for activation during differentiation and is required for embryonic development.

Yeast bromodomain-containing factors Bdf1/2 offer insights into the biological role of the BET family of transcriptional regulators, which is a promising target in cancer therapy.

Although the preinitiation complex for transcriptional initiation by RNA polymerase II contains highly conserved general transcription factors, there are kinetic and compositional differences in the initiation process among eukaryotic species.