Mediator Roles Going Beyond Transcription

Mediator is a large multiprotein complex conserved in eukaryotes and essential for transcription regulation. Recent advances suggest multiple functions of transcription-associated events that go beyond transcriptional processes per se, would help to understand the molecular mechanisms its mode action involvement various human pathologies. are related chromatin architecture, from nucleosome occupancy dynamics enhancer-promoter contacts genome organisation domains. forms phase-separated condensates on super-enhancers together with master factors, other coactivators, RNA polymerase II, signalling supporting model phase separation as an emerging mechanism nuclear functions. serves link between nucleotide-excision DNA repair recruitment machinery transcribed regions. Dysfunctions including lead severe diseases. Gaining understanding how these operate crowded context can be particularly challenging. key coactivator role regulation (Pol) II transcription. Despite intensive studies, underlying function remain fully understood. Novel findings have provided insights into relationship revealed connecting proposed involving condensates. developments field going se explain genome-organising self-associating domain identified by Micro-C yeast sequences interacting each other. protein or multisubunit interacts specific factors. Serves bridge basal acts structure one complexes. region PIC assembly located close TSS sufficient direct precise initiation. largest Pol subunit containing heptapeptide repeats. Phosphorylation post-translational modifications this important different steps cycle processing. regulatory metazoans bound factors at distances core promoter. Transcription enhancers produces noncoding enhancer RNAs contribute In yeast, regions named UASs. lacking defined 3D often repeated sequence elements, providing basis multivalent weak intermolecular interactions. IDR-containing proteins separate under physiological conditions enriched many biological Hi-C-based method analysis nucleosomal resolution, which micrococcal nuclease used instead restriction enzymes fragment chromatin. promoters depleted nucleosomes ensure accessibility proteins, machinery. evolutionarily pathway removes bulky and/or helix-distorting lesions, pyrimidine dimer photoproducts induced UV light (Box 2). local concentration fluid formation driven multivalent, cooperative, dynamic macromolecular Establishes biomolecular membraneless compartments, internal re-organisation rapid exchange kinetics. IDRs within involved assembled promoter It composed six GTFs (TFIIA, TFIIB, TFIID, TFIIH, TFIIE, TFIIF), Mediator. sequence-specific DNA-binding activator repressor protein, regulated cluster highly occupied Mediator, along coregulators These cell identity genes tumour oncogenes. ATP-dependent remodelling complex. genome-organisation Hi-C metazoans. Characterised high frequency interactions TAD, but insulation TADs. Architectural CTCF cohesin, subpathway NER, lesions strand interfere progression