Different SP1 binding dynamics at individual genomic loci in human cells

Abstract

Using a tamoxifen-inducible time-course ChIP-seq approach, we show that the ubiquitous transcription factor SP1 has different binding dynamics at its target sites in the human genome that are not correlated with SP1 occupancy levels at those sites. While ~70% of SP1 binding sites are located in promoter regions, loci with slow SP1 binding turnover are enriched in enhancer and Polycomb-repressed regions. Unexpectedly, SP1 sites with fast turnover times tend to have higher quality and more copies of the SP1 sequence motif. Different co-binding factors associate near SP1 binding sites depending on their binding kinetics and on their location at promoters or enhancers. For example, NFY and FOS are preferentially associated near promoter-bound SP1 sites with fast turnover, whereas DNA motifs of ETS and homeodomain proteins are preferentially observed at sites with slow turnover. At promoters but not enhancers, proteins involved in sumoylation and PML bodies associate more strongly with slow SP1 binding sites than with the fast-binding sites. The speed of SP1 binding turnover is not associated with nucleosome occupancy, and it is not necessarily coupled to higher transcriptional activity. These results with SP1 are in contrast from those of human TBP, indicating that there is no common mechanism affecting transcription factor binding kinetics.