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

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.

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 RNA-binding protein PTBP1 is recruited to sites near stop codons in retroviral and human mRNAs, shielding them from detection and degradation by the nonsense-mediated mRNA decay pathway.

RNA polymerase II generates numerous transcript isoforms, including transcripts initiating downstream of the START codon, that are efficiently degraded by the nonsense-mediated mRNA decay pathway.

Epigenetic transcriptional memory employs a novel regulatory strategy to create a heritable poised state by remodeling and repurposing complexes involved in active transcription.

Excess expression of the Gadd45 mRNA accounts for lethality when nonsense-mediated decay is lost in Drosophila and mammalian cells, revealing that this pathway is a critical gene regulatory mechanism.

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.

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.

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.