Genome-wide off-rates reveal how DNA binding dynamics shape transcription factor function

Wim J. de Jonge, Mariël Brok, Philip Lijnzaad, Patrick Kemmeren, Frank C.P. Holstege

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


Protein–DNA interactions are dynamic, and these dynamics are an important aspect of chromatin-associated processes such as transcription or replication. Due to a lack of methods to study on- and off-rates across entire genomes, protein–DNA interaction dynamics have not been studied extensively. Here, we determine in vivo off-rates for the Saccharomyces cerevisiae chromatin organizing factor Abf1, at 191 sites simultaneously across the yeast genome. Average Abf1 residence times span a wide range, varying between 4.2 and 33 min. Sites with different off-rates are associated with different functional characteristics. This includes their transcriptional dependency on Abf1, nucleosome positioning and the size of the nucleosome-free region, as well as the ability to roadblock RNA polymerase II for termination. The results show how off-rates contribute to transcription factor function and that DIVORSEQ (Determining In Vivo Off-Rates by SEQuencing) is a meaningful way of investigating protein–DNA binding dynamics genome-wide.

Original languageEnglish
Article numbere9885
JournalMolecular Systems Biology
Issue number10
Publication statusPublished - 1 Oct 2020


  • DNA binding dynamics
  • epigenetics
  • genomics
  • systems biology
  • transcription


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