Simple biochemical features underlie transcriptional activation domain diversity and dynamic, fuzzy binding to Mediator.

ABSTRACT: Gene activator proteins comprise distinct DNA-binding and transcriptional activation domains (ADs). Because few ADs have been described, we tested domains tiling all yeast transcription factors for activation in vivo and identified 150 ADs. By mRNA display, we showed that 73% of ADs bound the Med15 subunit of Mediator, and that binding strength was correlated with activation. AD-Mediator interaction in vitro was unaffected by a large excess of free activator protein, pointing to a dynamic mechanism of interaction. Structural modeling showed that ADs interact with Med15 without shape complementarity ('fuzzy' binding). ADs shared no sequence motifs, but mutagenesis revealed biochemical and structural constraints. Finally, a neural network trained on AD sequences accurately predicted ADs in h

SUBMITTER: Sanborn AL 

PROVIDER: S-EPMC8137143 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature