DNA Sequence Preferences of Transcriptional Activators Correlate More Strongly than Repressors with Nucleosomes

Summary Transcription factors (TFs) and histone octamers are two abundant classes of DNA binding proteins that coordinate the transcriptional program in cells. Detailed studies of individual TFs have shown that TFs bind to nucleosome-occluded DNA sequences and induce nucleosome disruption/repositioning, while recent global studies suggest this is not the only mechanism used by all TFs. We have analyzed to what extent the intrinsic DNA binding preferences of TFs and histones play a role in determining nucleosome occupancy, in addition to nonintrinsic factors such as the enzymatic activity of chromatin remodelers. The majority of TFs in budding yeast have an intrinsic sequence preference overlapping with nucleosomal histones. TFs with intrinsic DNA binding properties highly correlated with those of histones tend to be associated with gene activation and might compete with histones to bind to genomic DNA. Consistent with this, we show that activators induce more nucleosome disruption upon transcriptional activation than repressors.
Graphical Abstract Highlights ► We studied DNA-binding preferences for yeast nucleosomes and 137 TFs ► The majority of yeast TFs have intrinsic binding sequences similar to histones ► Activators have more similar intrinsic binding sequences than repressors to histones ► Activators compete more effectively with histones, disrupting nucleosomes formation