P300 Is an Obligate Integrator of Combinatorial Transcription Factor Inputs.

ABSTRACT: Transcription coactivators are proteins or protein complexes that mediate transcription factor (TF) function. However, they lack DNA binding capacity, prompting the question of how they engage target loci. Three non-exclusive hypotheses have been posited: coactivators are recruited by complexing with TFs, by binding histones through epigenetic reader domains, or by partitioning into phase-separated compartments through their extensive intrinsically disordered regions (IDRs). Using p300 as a prototypical coactivator, we systematically mutated its annotated domains and show by single-molecule tracking in live cells that coactivator-chromatin binding depends entirely on combinatorial binding of multiple TF-interaction domains. Furthermore, we demonstrate that acetyltransferase activity negati

SUBMITTER: Ferrie JJ 

PROVIDER: S-EPMC10245728 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature