Reference: de Jonge WJ, et al. (2020) Genome-wide off-rates reveal how DNA binding dynamics shape transcription factor function. Mol Syst Biol 16(10):e9885

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Abstract


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.

Reference Type
Journal Article | Research Support, Non-U.S. Gov't
Authors
de Jonge WJ, Brok M, Lijnzaad P, Kemmeren P, Holstege FC
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