Transcription activation domain structure correlates with gene expression levels

Transcription factors (TFs) are proteins that bind to specific DNA sequences and initiate transcription. TFs contain transcription activation domains (TAD) that are largely disordered and regulate their transcriptional activity. However, the properties that determine how TADs affect transcriptional activity remain poorly characterized. We hypothesize that despite their disorder, structural preferences within TADs can determine their activity. To test this hypothesis, we quantify TAD structure in live-cells using FRET microscopy. We find a strong correlation between TAD structure and their ability to induce protein expression. We further show that point mutations in TAD sequences that alter structure also alter TAD activity. Our findings suggest a novel mechanism for cellular regulation whereby the levels of gene expression can be modulated by IDR ensemble dimensions.