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Data from: Short activation domains control chromatin association of transcription factors

Fan, Vinson B.1

Published Jan 31, 2025; Updated Aug 21, 2025 on Dryad. https://doi.org/10.5061/dryad.41ns1rnqt

Data files

Jan 31, 2025 version files 592.54 MB
Aug 21, 2025 version files 655.91 MB

Abstract

Transcription factors regulate gene expression with DNA-binding domains (DBDs) and activation domains. Despite mounting evidence to the contrary, it is frequently assumed that DBDs are solely responsible for interacting with DNA and chromatin. Here, we used single-molecule tracking of transcription factors in living cells to show that short activation domains can control the fraction of molecules bound to chromatin. Stronger activation domains have higher bound fractions and longer residence times on chromatin. Furthermore, mutations that increase activation domain strength also increase chromatin binding. This trend was consistent in four different activation domains and their mutants. This effect further held for activation domains appended to three different structural classes of DBDs. Stronger activation domains with high chromatin-bound fractions also exhibited increased binding to the p300 coactivator in proximity-assisted photoactivation experiments. Taken together, these results suggest that activation domains play a major role in tethering transcription factors to chromatin, challenging the traditional view that the DBD is the sole driver of genome binding.