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Promoter-specific dynamics of TATA-binding protein association with the human genome

By Yuko Hasegawa, Jason D Lieb, Kevin Struhl

Posted 08 Jul 2019
bioRxiv DOI: 10.1101/696369 (published DOI: 10.1101/gr.254466.119)

Transcription factor binding to target sites in vivo is a dynamic process that involves cycles of association and dissociation, with individual proteins differing in their binding dynamics. The dynamics at individual sites on a genomic scale has been investigated in yeast cells, but comparable experiments have not been done in multicellular eukaryotes. Here, we describe a tamoxifen-inducible, time-course ChIP-seq approach to measure transcription factor binding dynamics at target sites throughout the human genome. As observed in yeast cells, the TATA-binding protein (TBP) typically displays rapid turnover at RNA polymerase (Pol) II-transcribed promoters, slow turnover at Pol III promoters, and very slow turnover at the Pol I promoter. Interestingly, turnover rates vary widely among Pol II promoters in a manner that does not correlate with the level of TBP occupancy. Human Pol II promoters with slow TBP dissociation preferentially contain a TATA consensus motif, support high transcriptional activity of downstream genes, and are linked with specific activators and chromatin remodelers. These properties of human promoters with slow TBP turnover differ from those of yeast promoters with slow turnover. These observations suggest that TBP binding dynamics differentially affect promoter function and gene expression, possibly at the level of transcriptional reinitiation/bursting.

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